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Jan 7th: Livesteaming Lecture and Discussion on HPPD and related disorders.

David S. Kozin

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References used in the process of creating the text and my introduction from the visiondisorder.org web site.

I wondered if my altered visual perception was a real problem. Is my altered visual experience a disorder possessing any clinical validity at all?

I apologize. I am lying. I am not laughing. This has been thirteen years for me and 30+ years for others.

Never do we question the disorder’s existence because it is so damn obvious. We are not a group of well-organized malingerers practicing to alter our EEG pattern in a stable way for measured “fake” quantitative EEGs or fudging psychophysics data. We didn’t sit in a room and decide on which medications would exacerbate the syndrome so researchers worldwide would write case reports about this problem. This is not a new problem.

If not the interest of the research and clinical community (besides a few notable exceptions, for which we owe so much), then what if an undergraduate was able to conduct a literature review and find a history for this syndrome with characteristics that are consistent, reliable, and possess diagnostic boundaries? Do you believe this syndrome is clinically significant?


Abraham, H. D. (1980). Psychiatric illness in drug abusers The New England Journal of Medicine, 302(15), 868-869.

Abraham, H. D. (1982). A chronic impairment of colour vision in users of LSD The British Journal of Psychiatry : The Journal of Mental Science, 140, 518-520.

Forty-six users of the hallucinogen lysergic acid diethylamide were compared with 31 controls on a test of colour discrimination an average of two years after their last exposure to the drug. Controls performed better than users, and LSD users without flashbacks performed better than users with flashbacks. An analysis of variance between the three groups was significant at P less than 0.001. This study suggests that some users of LSD may have a sustained or irreversible impairment in colour discrimination.

Abraham, H. D. (1983). Visual phenomenology of the LSD flashback Archives of General Psychiatry, 40(8), 884-889.

One hundred twenty-three persons with a history of LSD use were studied for the presence of the LSD flashback phenomenon and compared with 40 control subjects. A syndrome emerged that included ten distance visual disturbances. It had lasted for five years in half of the population, was treatable with benzodiazepines, exacerbated by phenothiazines, and precipitated by 19 different stimuli, most commonly emergence into a dark environment. Sensitivity to LSD as determined by flashbacks appears to divide the study sample into three discrete subgroups. There may be a genetic basis to LSD sensitivity.

Abraham, H. D., & Duffy, F. H. (1996). Stable quantitative EEG difference in post-LSD visual disorder by split-half analysis: Evidence for disinhibition Psychiatry Research, 67(3), 173-187.

Hallucinogen persisting perceptual disorder (HPPD) may follow the ingestion of LSD or other hallucinogens in a subset of users. It is characterized by chronic, intermittent or constant visual hallucinations of many sorts persisting beyond the period of acute drug effects. We studied 44 LSD-induced HPPD subjects and 88 matched controls to search for spectral and evoked potential differences using quantitative EEG (qEEG). HPPD subjects demonstrated faster alpha frequency and shorter VER (visual evoked response) latency, consistent with prior animal and human data on response to acute LSD administration which suggest LSD-induced cortical disinhibition. AER (auditory evoked response) latency was prolonged consistent with a differential LSD effect upon visual and auditory systems. The exploratory T-statistic significance probability mapping (T-SPM) technique demonstrated HPPD-control differences mostly involving temporal and left parietal scalp regions, confirmed by a split-half analysis. Significant variables were all derived from the long latency flash VER and click AER. None were derived from spectral analyzed EEG data. Canonical correlation between SPM-derived measures and variables reflecting disease severity was highly significant. A between-group stepwise discriminant analysis based upon a full set of qEEG measures demonstrated 87% prospective classification success by jackknifing and 88% success in a separate split-half analysis.

Abraham, H. D., & Duffy, F. H. (2001). EEG coherence in post-LSD visual hallucinations Psychiatry Research, 107(3), 151-163.

LSD use in certain individuals may result in chronic visual hallucinations, a DSM-IV syndrome known as hallucinogen persisting perception disorder (HPPD). We studied 38 HPPD subjects with a mean of 9.7 years of persistent visual hallucinations and 33 control subjects. Measures of local and medium distance EEG spectral coherence were calculated from all subjects. Coherence, a measure of spectral similarity over time, may estimate cortical coupling. In the eyes-open state in HPPD subjects, widespread reduction of coherence was noted. However, upon eye closure, the occipital region demonstrated augmented regional coherence over many frequencies but with reduced coherence of the occipital region to more distant regions. This occipital coherence increase correlated with previously reported shortened occipital visual evoked potential latency for HPPD subjects. We speculate from coherence and known clinical and psychophysical data that, in HPPD, there is widespread cortical inhibition in the eyes-opened state, but localized and isolated occipital disinhibition upon eye closure, a state known to facilitate hallucinatory experiences. An analogy is drawn to findings in the interictal and ictal epileptic focus. In HPPD, we speculate that occipital EEG hypersynchrony resulting from increased regional coherence, when coupled with relative isolation of visual cortex, especially upon eye closure, facilitates hallucinations and illusions.

Abraham, H. D., & Mamen, A. (1996). LSD-like panic from risperidone in post-LSD visual disorder Journal of Clinical Psychopharmacology, 16(3), 238-241.

Risperidone, a novel antipsychotic agent, is an antagonist of postsynaptic serotonin-2 and dopamine D2 receptors. In certain individuals, the hallucinogenic drug lysergic acid diethylamide (LSD) is associated with apparently lifelong continuous visual disturbances, characterized in DSM-IV as hallucinogen-persisting perception disorder (HPPD). Because the hallucinogenic mechanism of LSD is known to act in part at postsynaptic serotonin-2 receptors, it is noteworthy that three HPPD patients treated with risperidone reported an exacerbation of LSD-like panic and visual symptoms. We conclude that HPPD may be a relative contraindication for the use of risperidone.

Abraham, H. D. (1996). The anxious substance abuser and the anxious clinician. In J. M. Ellison, & J. M. Ellison (Eds.), Integrative treatment of anxiety disorders. (pp. 275-304). Washington, DC US: American Psychiatric Association.

studies of order of onset in patients with both anxiety and substance use disorders [alcohol and anxiety disorders, psychostimulant drugs and panic attacks, cannabis and panic attacks, LSD and panic disorder, sedatives and generalized anxiety disorder] / treatment of the dually diagnosed patient [acute phase, subacute phase, chronic phase] (PsycINFO Database Record © 2008 APA, all rights reserved)

Abraham, H. D. (2001). Reply: New hope for hallucinogen-induced persistent perceptual disorder? Journal of Clinical Psychopharmacology, 21(3), 344-344.

Comments on G. Aldurra and J. W. Crayton’s (see record 200117884-013) description of a 17-yr-old male who showed improvement of hallucinogen persisting perception disorder (HPPD) after treatment with a combination of fluoxetine and olanzapine. H. D. Anderson states that it is not clear how 2 5-hydroxytryptamine-sub-2 (5-HT-sub-2) antagonists, risperidone and olanzapine, exert opposite clinical effects on HPPD, except that the former is a more potent antagonist than the latter by an order of magnitude. In light of the finding, a controlled trial is warranted. (PsycINFO Database Record © 2008 APA, all rights reserved)

Abraham, H. D. (2007). Psychedelic medicine: New evidence for hallucinogenic substances as treatments (2 volumes). Psychiatric Times, 24(13), 30-30.

The article reviews the book “Psychedelic Medicine: New Evidence for Hallucinogenic Substances As Treatments,” edited by Michael J. Winkelman and Thomas B. Roberts.

Abraham, H. D., Aldridge, A. M., & Markel, H. (1994). ‘LSD and post-hallucinogen perceptual disorder’: Comment. United Kingdom: Blackwell Publishing.

Replies to the comment by J. S. Madden (see record 1995-09917-001) on the review by H. D. Abraham and A. M. Aldridge (see record 1994-13795-001) that attributes the 1st description of post-hallucinogen perceptual disorder (PHPD) to 1958. The authors express gratitude to Madden for reminding them of the pioneering work of R. A. Sandison et al (1954), C. Elkes et al (1955), and H. A. Cooper (1955). Madden’s idea that depression has been overlooked in Ss with PHPD following LSD is supported by preliminary data from an ongoing study by H. D. Abraham and A. M. Aldridge. 59 Ss with PHPD reported a lifetime prevalence for affective disorder more than double that in substance-abusing controls without comparable LSD use. Assessments in 375 outpatients with major depressive disorder revealed that while several drugs (alcohol and stimulants) appeared to follow depression, LSD was the only drug the use of which appeared contemporaneous with the onset of depression. (PsycINFO Database Record © 2008 APA, all rights reserved)

Abraham, H. D., Anderson, C., & Lee, D. (1997). Somatization disorder in sphincter of oddi dysfunction. Psychosomatic Medicine, 59(5), 553-557.

Examined whether women with Sphincter of Oddi dysfunction (SOD) were overrepresented on measures of somatization, sexual and physical abuse, socially compliant attitudes, and familial psychiatric illness. 33 women with SOD (mean age 45.4 yrs) were matched to 33 normal controls by age, sex, and race, and, with a case-controlled cross-sectional questionnaire, compared the groups on the study variables. SOD Ss exhibited excessive nongastroenterological somatic complaints compared with controls. There was a statistical increase in reports of childhood sexual, but not physical, abuse in the SOD Ss compared with controls. The severity of the abuse correlated strongly with the severity of somatic complaints. There were no differences in social desirability attitudes or family psychiatric histories of the 2 groups. It is concluded that SOD is associated with a high degree of somatization in adulthood, and a mean rate more than 4 times that of controls in self-reports of sexual abuse in childhood. The severity of childhood sexual abuse is correlated with the severity of somatization in later life. A psychological model for this disorder is suggested by the data. Increased psychiatric attention is indicated in the treatment of women with this disorder. (PsycINFO Database Record © 2008 APA, all rights reserved)

Abraham, H. D., & Fava, M. (1999). Order of onset of substance abuse and depression in a sample of depressed outpatients. Comprehensive Psychiatry, 40(1), 44-50.

Examines whether specific types of drug abuse precede or follow the onset of depression. A retrospective, case-controlled assessment of the drug and depressive history of depressed outpatients was conducted. 375 18-65 yr olds with major depressive disorder were evaluated for comorbid drug dependence using the Structured Clinical Interview for Diagnostic and Statistical Manual of Mental Disorders-III-Revised (DSM-III-R) and grouped into homogeneous classes of drug dependence including alcohol, cannabis, cocaine, amphetamine, LSD, hypnosedative, opiate, and polysubstance use. For each specific type of drug abuse, the percent of depressed Ss, their age of onset of depression and of specific drug abuse, and the mean number of lifetime depressive episodes were determined. Alcohol dependence followed the onset of 1st life depression by 4.7 yrs. Among polydrug-dependent Ss, each drug abused followed the onset of depression, except for LSD which coincided with the onset of depression. Among polydrug users, cocaine dependence occurred 6.8 yrs after the 1st major depressive episode and alcohol dependence 4.5 yrs after the onset of depression. Opiate and sedative users had the least number of lifetime depressive episodes (3.7), and LSD and cocaine users had the greatest number (12.2). (PsycINFO Database Record © 2008 APA, all rights reserved)

Abraham, H. D., Wolf, E., Abraham, H. D., & Wolf, E. (1988). Visual disturbances associated with lsd. Journal of Abnormal Psychology, 97, 443-447.

Abruzzi, W. (1977). Drug-induced psychosis The International Journal of the Addictions, 12(1), 183-193.

Adamec, C., Pihl, R. O., & Leiter, L. (1976). An analysis of the subjective marijuana experience The International Journal of the Addictions, 11(2), 295-307.

Two hundred and thirty-six marijuana users who volunteered for a study in which they would use the drug were administered a Drug History and a Marihuana Effects Questionnaires. In addition to obtaining descriptive information of drug experiment volunteers and a factor analysis of the marijuana experience, the relationship between experience and effect variables were studied. The results of the above analysis suggest that the “typical” subject in marijuana experiments is not a “typical” user, that the marijuana experience is verbally definable, and that prior expectancies and histories of effect alter the experience.

Alcántra, A. G. (1998). Is there a role for the ?-sub-2 antagonism in the exacerbation of hallucinogen-persisting perception disorder with risperidone? Journal of Clinical Psychopharmacology, 18(6), 487-488.

Claims that the possible exacerbation of hallucinogen-persisting perception disorder with risperidone may be a consequence of its stimulant properties, secondary to an enhancement of the noradrenergic and serotonergic transmission. (PsycINFO Database Record © 2008 APA, all rights reserved)

Aldurra, G., & Crayton, J. W. (2001). Improvement of hallucinogen persisting perception disorder by treatment with a combination of fluoxetine and olanzapine: Case report. Journal of Clinical Psychopharmacology, 21(3), 343-344.

A diagnosis of hallucinogen-induced persistent perceptual disorder with concurrent depression was made for a 17-yr-old male with a history of polysubstance abuse, primarily involving LSD. This patient showed a marked exacerbation of symptoms while taking risperidone and showed an attenuation of symptoms with a combination of fluoxetine and olanzapine. (PsycINFO Database Record © 2008 APA, all rights reserved)

Alldredge, B. K., Lowenstein, D. H., & Simon, R. P. (1989). Seizures associated with recreational drug abuse Neurology, 39(8), 1037-1039.

We retrospectively identified 49 cases of recreational drug-induced seizures in 47 patients seen at the San Francisco General Hospital between 1975 and 1987. Most patients experienced a single generalized tonic-clonic seizure associated with acute drug intoxication, but 7 patients had multiple seizures and 2 patients developed status epilepticus. The recreational drugs implicated were cocaine (32 cases), amphetamine (11), heroin (7), and phencyclidine (4). A combination of drugs was responsible in 11 cases. Seizures occurred independent of the route of administration, and occurred in both first-time and chronic abusers. Ten patients (21%) reported having had prior seizures, all with a close temporal association with drug abuse. Other than 1 patient who developed prolonged status epilepticus that caused a fixed neurologic deficit, most patients had no obvious short-term neurologic sequelae.

Amler, G. (1971). Problems of present-day intoxicating drugs [Zur Problematik der modernen Rauschmittel ] Deutsche Krankenpflegezeitschrift, 24(1), 11-17.

Amphetamines, barbiturates, LSD and cannabis: Their use and misuse (1970). Reports on Public Health and Medical Subjects, 124, 1-75.

Angrist, B., Smith, M., Adler, L., Peselow, E., Reitano, J., & Rotrosen, J. (1988). Preliminary studies of clonidine in psychotic patients Journal of Neural Transmission, 71(2), 115-121.

Twelve psychotic patients received a mean dose of 3.3 mg/day of clonidine. In four clonidine was the only treatment and in the remaining eight clonidine was superadded to a neuroleptic regimen after symptomatology was stable. Clonidine caused reduction of scores for both productive psychotic symptoms and anxiety. Negative symptoms were unaffected. These findings are discussed with respect to the small magnitude of the effects, questions as to specificity of the effects and methodologic limitations of this pilot study.

Bartko, G., Trixler, M., Bitter, I., Degrell, I., Furedi, J., Faludi, G., et al. (2006). Switching patients with schizophrenia to ziprasidone from conventional or other atypical antipsychotics [Valtas ziprasidonra hagyomanyos vagy mas atipusos antipszichotikumokrol szkizofreniaban szenvedo betegekben ] Neuropsychopharmacologia Hungarica : A Magyar Pszichofarmakologiai Egyesulet Lapja = Official Journal of the Hungarian Association of Psychopharmacology, 8(4), 201-209.

OBJECTIVES: The aim of the study was to assess the efficacy, tolerability and safety of ziprasidone in patients with schizophrenia who were already treated with conventional or other atypical antipsychotics that had to be switched due the lack of efficacy or bad tolerance. METHODS: The study was a 12-week, open label, multicenter, non comparative trial on oral ziprasidone. 106 patients with DSM-IV schizophrenia were switched to ziprasidone from their previous antipsychotic without a washout phase. The study required fixed dosing with ziprasidone. For the first week the patient received 80 mg of study drug daily, followed for 3 weeks 120 mg/day. Subsequently for 8 weeks either 80 mg, or 120 mg, or 160 mg total daily dose could be given at the discretion of the investigator. Baseline and outcome assessment included Positive and Negative Syndrome Scale (PANSS), Clinical Global Impression Severity of Illness Subscale (CGI-S) and Global Improvement Subscale (CGI-I), Calgary Depression Scale (CAD), Hamilton Depression Scale (HAMD), Drug Attitude Inventory (DAI), Simpson Angus Extrapyramidal Symptoms Rating Scale (SAS) and Barnes Akathisia Rating Scale (BARS). Changes in overall body weight were also evaluated. RESULTS: After 12 weeks on ziprasidone therapy, significant improvements were observed on all major symptoms measures and subscales. 34 (51,5%) patients (ITT) were rated much or very much improved on CGI-I at week 12. The mean SAS score significantly reduced during the ziprasidone treatment period (p

Batzer, W., Ditzler, T., & Brown, C. (1999). LSD use and flashbacks in alcoholic patients Journal of Addictive Diseases, 18(2), 57-63.

Lysergic Acid Diethylamide (LSD) is a hallucinogenic drug that received considerable attention in the 1960′s and early 1970′s. It produced a wide variety of psychological phenomena, including a variety of perceptual disturbances which would manifest among some users long after the drug had left the system. These phenomena were commonly referred to as “flashbacks” and may have been largely responsible for the drug falling out of favor among recreational drug users. This report describes histories of LSD use among alcoholism treatment facility inpatients and reports specific characteristics of flashbacks and the degree of subjective distress experienced during flashbacks. Findings indicate a statistically significant relationship between number of doses and incidence of flashbacks.

Becker, H. S. (1967). History, culture and subjective experience: An exploration of the social bases of drug-induced experiences Journal of Health and Social Behavior, 8(3), 163-176.

Bennet, G. (1968). Lsd: 1967 The British Journal of Psychiatry : The Journal of Mental Science, 114(515), 1219-1222.

Biener, K. (1974). Drug consumption in young persons. comparative study in relation to sex [il consumo di droga nei giovani. Studio comparativo in rapporto al sesso ] Minerva Medica, 65(54), 2908-2915.

Bogdanoff, B., Rorke, L. B., Yanoff, M., & Warren, W. S. (1972). Brain and eye abnormalities. possible sequelae to prenatal use of multiple drugs including LSD American Journal of Diseases of Children (1960), 123(2), 145-148.

Bourne, P. G. (1974). Polydrug abuse–considerations in a national strategy The American Journal of Drug and Alcohol Abuse, 1(2), 147-158.

Brannan, S. K., Mallinckrodt, C. H., Brown, E. B., Wohlreich, M. M., Watkin, J. G., & Schatzberg, A. F. (2005). Duloxetine 60 mg once-daily in the treatment of painful physical symptoms in patients with major depressive disorder Journal of Psychiatric Research, 39(1), 43-53. doi:10.1016/j.jpsychires.2004.04.011

BACKGROUND: While emotional symptoms such as depressed mood and loss of interest have traditionally been considered to constitute the core symptoms of major depressive disorder (MDD), the prevalence and importance of painful physical symptoms such as back pain, abdominal pain, and musculoskeletal pain is becoming increasingly appreciated. Antidepressants possessing dual serotonin/norepinephrine (5-HT/NE) reuptake inhibition may demonstrate greater efficacy in the alleviation of pain. The efficacy of duloxetine, a balanced and potent dual reuptake inhibitor of 5-HT and NE, was evaluated within a cohort of depressed patients with associated painful physical symptoms. METHODS: In this multicenter, double-blind, placebo-controlled study, patients meeting DSM-IV criteria for MDD were randomized to receive placebo (N=141) or duloxetine 60 mg QD (N=141). Patients were required to have a 17-item Hamilton Rating Scale for Depression (HAMD17) total score 15, a Clinical Global Impression of Severity (CGI-S) score 4, and a Brief Pain Inventory (BPI) Average Pain score 2 at baseline. The primary efficacy measure was the BPI Average Pain score, while secondary measures included other BPI items, the HAMD17 total score, CGI-S, the Patient Global Impression of Improvement (PGI-I) scale, Visual Analog Scales (VAS) for pain, and the Symptom Questionnaire, Somatic Subscale (SQSS). Safety was evaluated by recording treatment-emergent adverse events (spontaneously reported), vital signs, and laboratory analytes. RESULTS: Mean changes in BPI Average Pain for duloxetine- and placebo-treated patients differed significantly at most visits, but only approached significance at endpoint p=0.066. For the main effect of treatment (pooling all visits), significant advantages for duloxetine-treated patients were found in 10 of 11 assessed BPI pain severity and pain interference items, in addition to VAS overall pain and back pain. Mean changes in pain measures for duloxetine-treated patients corresponded to improvements of 25-50%, compared with 19-39% for placebo. Mean changes at endpoint in depression rating scales (HAMD17, CGI-S, PGI-I) did not differ significantly between duloxetine and placebo treatment groups due to unusually high placebo response. The magnitude of placebo treatment effects (as measured by HAMD17 total score and Maier subscale) was significantly smaller in patients with 1 previous depressive episode, compared to those patients with no previous episodes. In patients with 1 previous depressive episode the advantage of duloxetine over placebo was similar to previous studies. Rates of discontinuation due to adverse events were 14.2% vs. 2.1% for duloxetine and placebo, respectively p

Businco, L. (1970). The great medico-social problems of neuropsychiatry: Drugs [i grandi problemi medico-sociali della neuropsichiatria: la droga ] Il Policlinico.Sezione Pratica, 77(29), 950-954.

Caplan, L. R., Hier, D. B., & Banks, G. (1982). Current concepts of cerebrovascular disease–stroke: Stroke and drug abuse Stroke; a Journal of Cerebral Circulation, 13(6), 869-872.

Carella, A. (1967). Medico-legal importance of the increasing use of diethylamide of lysergic acid (LSD) [interesse medico-legale per il crescente uso della dietilamide dell'acido lisergico (LSD) ] Zacchia, 3(2), 231-248.

Cezayirli, S. E., Little, S. C., & Estock, R. (1975). Correlation of drug abuse, psychiatric diagnosis and EEG findings Journal of the Medical Association of the State of Alabama, 44(11), 616-621.

Charles-Nicolas, A. J., & Caroli, F. (1977). Elements of answers to questions frequently asked the general practitioner on the subject of the use of drugs [Element de reponses aux questions frequement posees au praticien en matiere de consommation de drogues ] La Semaine Des Hopitaux : Organe Fonde Par l’Association d’Enseignement Medical Des Hopitaux De Paris, 53(16), 919-922.

Commissaris, R., Lyness, W. H., Cordon, J. J., Moore, K. E., & Rech, R. H. (1980). The effects of d-lysergic acid diethylamide (LSD), 2,5-dimethoxy-4-methylamphetamine (DOM) and d-amphetamine on operant responding in control and 6-hydroxydopamine-treated rats Pharmacology, Biochemistry, and Behavior, 13(5), 621-626.

The purpose of the present study was to determine the role of central catecholaminergic neuronal systems in the effects of LSD, DOM and d-amphetamine on fixed ratio (FR) operant responding in rats. Food-deprived male rats were trained to press a bar for food reinforcement on a FR-40 schedule. Control responding on this schedule is characterized by a rapid, constant rate of responding (approximately 100 responses/min) throughout a 40 min test session. LSD and DOM, as with other hallucinogens, produced dose-dependent periods of nonresponding or “pausing,” followed by reinstatement of responding at or near the control rate. Administration of the non-hallucinogen, d-amphetamine, did not produce “pausing,” but caused the response rate to slow and become erratic. In animals pretreated intraventricularly with 6-hydroxydopamine (6-OHDA; 200 micrograms/10 microliter X 2), the response to LSD and DOM was unchanged, while the response to d-amphetamine was significantly diminished. The neurotoxin significantly decreased brain catecholamines to less than 25 percent of control in al regions examined, without altering 5-HT concentrations in these same regions. These data demonstrate that the effects of LSD and DOM on FR-40 responding are quite different from those of d-amphetamine, and that this difference may be due to the extent of catecholamine involvement in the effects of these agents.

Commissaris, R. L., Lyness, W. H., & Rech, R. H. (1981). The effect of d-lysergic acid diethylamide (LSD), 2,5-dimethoxy-4-methylamphetamine (DOM), pentobarbital and methaqualone on punished responding in control and 5,7-dihydroxytryptamine-treated rats Pharmacology, Biochemistry, and Behavior, 14(5), 617-623.

The purpose of the present study was to determine the role of central 5-hydroxytryptamine (5-HT) neuronal systems in the effects of d-lysergic acid diethylamide (LSD), 2,5-methoxy-4-methylamphetamine (DOM), pentobarbital (PB) and methaqualone (MQ) on punished responding in rats. Water-deprived rats were trained to drink from a tube that was electrified at intervals (variable interval 21 sec; 0.03 mA current intensity), electrification being signalled by a tone. In daily 10-min control sessions, these animals accepted a relatively constant number of shocks; water consumption was also quite stable. At maximally effective doses PB, and to a lesser extent MQ, produced large (400-600 percent of control) increases in punished responding with little decrease in water intake. Higher doses of these agents produced a significant depression of unpunished responding (water intake). The hallucinogens, on the other hand, produced only moderate (125-175 percent of control) increases in the number of shock received, yet a similar depression of unpunished responding. Selective destruction of 5-HT neurons by intracerebroventricular administration of the neurotoxin 5,7-dihydroxytryptamine per se produced little change in the number of shocks received or water consumed in controls sessions. This destruction of 5-HT neurons failed to alter the effects of PB or MQ on punished or unpunished responding. The increase in punished responding produced by the hallucinogens, however, was blocked by this destruction of 5-HT neurons. Furthermore, the capacity of the hallucinogens to decrease water intake was significantly potentiated by the neurotoxin pretreatment. These data demonstrate that the effects of the hallucinogens LSD and DOM on conditioned suppression are quite different from those of PB and MQ, and that this difference may be due to the extent of 5-HT involvement in the effects of these agents.

Dalmau, A., Bergman, B., & Brismar, B. (1999). Psychotic disorders among inpatients with abuse of cannabis, amphetamine and opiates. do dopaminergic stimulants facilitate psychiatric illness? European Psychiatry : The Journal of the Association of European Psychiatrists, 14(7), 366-371.

We have studied the occurrence of dual diagnoses (psychoses as well as abuse of either amphetamine, cannabis or opiates) during a 15-year period, among patients treated at Huddinge Hospital, Stockholm, Sweden. The purpose of the study is to evaluate if the different drugs were coupled to different rates of psychiatric co-morbidity. During the period in question, 461, 425 and 371 different patients respectively had been admitted at least once due to dependency on amphetamine, cannabis and opiates. Approximately 30% of the patients with a pure abuse of amphetamine or cannabis and less than 6% of the opiate abusers had been diagnosed at least once with any of the psychoses studied. Comparing the frequency of psychoses among mixed and pure abusers of illegal drugs, with and without a concomitant abuse of alcohol, we found that the co-morbidity rate for mixed opiate abusers increased significantly from 7.2 to 20.2% when alcohol abuse was also present. For abusers of amphetamine and cannabis (both pure and mixed), no differences in co-morbidity rates were seen when an abuse of alcohol was added to that of the drugs. It is difficult to find an explanation for the significant difference between the co-morbidity of pure abuse of amphetamine or cannabis on the one hand and opiates on the other. In conclusion, our findings show that the distribution of psychotic illness is high among abusers of amphetamine and cannabis, in contrast to the generally lower co-morbidity among abusers of opiates. Although these findings are consistent with earlier studies that have shown a propensity for developing psychoses among abusers of amphetamine and cannabis, one should bear in mind that this study is based on inpatients, and is not necessarily representative for all abusers of the drugs in question.

Davis, W. M. (1982). LSD or DOB? The American Journal of Psychiatry, 139(12), 1649.

Delliou, D. (1980). Bromo-DMA: New hallucinogenic drug The Medical Journal of Australia, 1(2), 83.

Delva, N. J., Chang, A., Hawken, E. R., Lawson, J. S., & Owen, J. A. (2002). Effects of clonidine in schizophrenic patients with primary polydipsia: Three single case studies Progress in Neuro-Psychopharmacology & Biological Psychiatry, 26(2), 387-392.

A pilot study was conducted in schizophrenic patients with primary polydipsia to determine the tolerability of adding clonidine to an existing antipsychotic drug regimen and to seek evidence of an antidipsic effect. Three patients with chronic schizophrenia and primary polydipsia underwent open controlled prospective trials of treatment with clonidine in doses of up to 800 microg/day. The trials lasted from 2 to 5 months each, and analysis of variance was used to test for changes in dependent variables on a case-by-case basis. Blood pressure and pulse declined significantly in a dose-dependent manner, but fluid intake, as assessed by measurements of weight and 24-h urine volume, was not affected. Hypotension and bradycardia limited the extent to which the dose of clonidine could be increased. The lack of evident effect of clonidine on polydipsia in this small sample and the inconsistent results of two other recent studies of clonidine in patients with schizophrenia and primary polydipsia provide little overall support for the effectiveness of clonidine treatment in primary polydipsia associated with schizophrenia.

Dependence on LSD and other hallucinogenic drugs (1967). JAMA : The Journal of the American Medical Association, 202(1), 141-144.

Dezelsky, T. L., Toohey, J. V., & Shaw, R. S. (1985). Non-medical drug use behaviour at five united states universities: A 15-year study Bulletin on Narcotics, 37(2-3), 49-53.

A survey carried out in 1970, 1973, 1976, 1980 and 1984 by means of a questionnaire at five American universities, which involved a total of 4,171 students, showed an increase in the use of cocaine, cannabis, hallucinogens, sedatives, amphetamines and alcohol. Cocaine use increased from 2.7 per cent in 1970 to 30 per cent in 1984, while cannabis use almost doubled during that period. The survey found that intercollegiate athletes used significantly more anabolic steroids than non-athletes, but with regard to the use of other substances the athletic students did not differ significantly from non-athletic students.

DiBenedetto, M. (1976). Electrodiagnostic evidence of subclinical disease states in drug abusers Archives of Physical Medicine and Rehabilitation, 57(2), 62-66.

One hundred drug abusers, free of clinical signs or symptoms of disease, were examined by electrodiagnostic techniques. Sensory conduction of median, ulnar and sural nerves was evaluated in terms of latency, velocity and amplitude of evoked potential. Motor nerve latencies and conduction velocities of median, ulnar and personeal nerves were determined. Definite changes in the evoked sensory potentials of median and sural nerves of subjects using heroin or LSD were demonstrated. The sensory amplitude changes were suggestive of axonal degreneration because of normal duration. Maximum motor conduction velocity was abnormal in one patient who admitted using a variety of drugs; five heroin and two barbiturate users showed dispersed motor responses suggesting small fiber involvement. No abnormality could be shown in marjuana smokers. Signifcance of these findings is explained, emphasizing important potential for recognition of subclinical abnormalities and the opportunity for disease prevention.

Does risperidone exacerbate hallucinogen-persisting perception disorder?(1998). Brown University Psychopharmacology Update, 9(2), 8.

Reports on the findings of a case study published in a 1997 issue of the `Journal of Clinical Psychopharmacology,’ about the effectiveness of risperidone in exacerbating hallucinogen-persisting perception disorder. Patient’s medical background; Drug abuse history; Contraindications of risperidone.

Duehn, W. D. (1978). Covert sensitization in group treatment of adolescent drug abusers The International Journal of the Addictions, 13(3), 485-491.

Seven self-referred males with long-standing histories of excessive use of amphetamines, LSD, and marijuana participated in an experiment dealing with the behavioral procedures of covert sensitization in group treatment. LSD usage did not change during a 14-week precovert-sensitization treatment program. The group then received covert sensitization in 11 sessions within a 6-week period, with all members reporting no LSD usage or desire to take LSD. A 6 to 18-month follow-up indicated that six subjects had not taken LSD. Two subjects reported self-administration of covert sensitization procedures at home to develop aversions to other drugs and were completely drug-free. The seventh subject could not be located. The practical advantages of using covert sensitization procedures in group treatment of drug users within the school setting are discussed.

Duncan, J. W. (1974). Persisting psychotic states in adolescent drug users. Child Psychiatry and Human Development, 5(1), 51-62.

Dunlop, B. W., Papp, L., Garlow, S. J., Weiss, P. S., Knight, B. T., & Ninan, P. T. (2007). Tiagabine for social anxiety disorder Human Psychopharmacology, 22(4), 241-244. doi:10.1002/hup.846

Tiagabine, a selective gamma-aminobutyric acid (GABA) reuptake inhibitor was evaluated for the treatment of patients with social anxiety disorder (SAD). Adults with SAD received open-label tiagabine 4-16 mg per day for 12 weeks. Intent-to-treat data are available for 54 patients with improvement demonstrated in Liebowitz Social Anxiety Scale, Clinician Global Impression-Severity (CGI-S) and -Improvement (CGI-I), Social Phobia Inventory, and Sheehan Disability Scale scores. In all, 40.7% (22/54) of the intent to treat sample and 63.0% (17/27) of the completer sample were considered CGI responders (CGI-I score of one or two). Tiagabine was generally well tolerated. Results of this pilot study suggest that tiagabine may be an option for the treatment of patients with SAD. Larger, controlled studies are required to fully elucidate the potential of tiagabine for the treatment of SAD.

Dyck, E. (2005). Flashback: Psychiatric experimentation with LSD in historical perspective Canadian Journal of Psychiatry.Revue Canadienne De Psychiatrie, 50(7), 381-388.

In the popular mind, d-lysergic acid diethylamide (LSD) research in psychiatry has long been associated with the CIA-funded experiments conducted by Ewen Cameron at the Allen Memorial Institute in Montreal, Quebec. Despite this reputation, a host of medical researchers in the post World War II era explored LSD for its potential therapeutic value. Some of the most widespread trials in the Western world occurred in Saskatchewan, under the direction of psychiatrists Humphry Osmond (in Weyburn) and Abram Hoffer (in Saskatoon). These medical researchers were first drawn to LSD because of its ability to produce a “model psychosis.” Their experiments with the drug that Osmond was to famously describe as a “psychedelic” led them to hypothesize and promote the biochemical nature of schizophrenia. This brief paper examines the early trials in Saskatchewan, drawing on hospital records, interviews with former research subjects, and the private papers of Hoffer and Osmond. It demonstrates that, far from being fringe medical research, these LSD trials represented a fruitful, and indeed encouraging, branch of psychiatric research occurring alongside more famous and successful trials of the first generation of psychopharmacological agents, such as chlropromazine and imipramine. Ultimately, these LSD experiments failed for 2 reasons, one scientific and the other cultural. First, in the 1950s and early 1960s, the scientific parameters of clinical trials shifted to necessitate randomized controlled trials, which the Saskatchewan researchers had failed to construct. Second, as LSD became increasingly associated with student riots, antiwar demonstrations, and the counterculture, governments intervened to criminalize the drug, restricting and then terminating formal medical research into its potential therapeutic effects.

Dyer, C. (2002). NHS settles claim of patients treated with LSD BMJ (Clinical Research Ed.), 324(7336), 501.

Eiser, J. R., Gossop, M., & van der Pligt, J. (1980). Drug attitudes and discrimination between drugs among a group of english schoolchildren Drug and Alcohol Dependence, 5(1), 57-62.

This study investigates the attitudes of a group of 185 London schoolchildren towards a number of legal and illegal drugs, and examines the ways in which they discriminate between these drugs. Heroin and LSD were seen as the most dangerous drugs, and alcohol and cigarettes as the safest. Subjects who had a negative attitude towards drugs in general regarded cannabis, amphetamines, alcohol and tobacco as more dangerous than subjects with a neutral or pro-drug attitude. There was also a sex difference: boys claimed to know more about drugs, were more likely to know a cannabis user and to have been “really drunk” than the girls. The implications of these results for drug and alcohol education programmes are discussed.

El-Mallakh, R., & Abraham, H. D. (2007). MDMA (ecstasy). Annals of Clinical Psychiatry, 19(1), 45-52.

Background. 3,4-Methylenedioxymethamphetamine (MDMA or Ecstasy) is a synthetic amphetamine analogue that is recreationally used to obtain a psychological effect of enhanced affiliative emotional response. Its use in Western countries appears to be increasing, particularly among young individuals. Methods. Pertinent basic and clinical literature is critically reviewed. Results. A significant body of literature suggests that the patterns of MDMA use differ from traditional drugs of abuse, with relatively uncommon dependence and escalation of dosage. Nonetheless, MDMA is also neurotoxic with significant deleterious effects on serotonergic neurons, memory, and mood. Despite this, there is a dearth of treatment strategies for both acute intoxication and consequences of longer term use. Conclusions. MDMA is an important drug of abuse that has a wide range of adverse consequences. [ABSTRACT FROM AUTHOR]; Copyright of Annals of Clinical Psychiatry is the property of Taylor & Francis Ltd and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder’s express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts)

Espiard, M., Lecardeur, L., Abadie, P., Halbecq, I., & Dollfus, S. (2005). Hallucinogen persisting perception disorder after psilocybin consumption: A case study. European Psychiatry, 20(5), 458-460.

Abstract: The recurrence of flashbacks without acute or chronic hallucinogen consumption has been recognized in the DSM IV criteria as the hallucinogen persisting perception disorder (HPPD). Perceptual disturbances may last for 5 years or more and represent a real psychosocial distress. We reported here a case of a 18-year-old young man presenting HPPD after a mixed intoxication with psylocibin and cannabis. This report shows symptomatic recurrences persisting more than 8 months. Various differential diagnoses were evoked and our therapeutic strategies were described. [Copyright 2005 Elsevier]; Copyright of European Psychiatry is the property of Elsevier Science Publishing Company, Inc. and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder’s express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts)

Farnsworth, D. L. (1968). The drug problem among young people. use of both LSD and marijuana entails significant risk Rhode Island Medical Journal, 51(3), 179-82 passim.

Favazza, A. R., & Domino, E. F. (1969). Recurrent LSD experience (flashbacks) triggered by marihuana University of Michigan Medical Center Journal, 35(4), 214-216.

Fischer, J., & Taschner, K. L. (1991). Flashback following use of cannabis–a review [Flashback nach Cannabiskonsum--eine Ubersicht ] Fortschritte Der Neurologie-Psychiatrie, 59(11), 437-446.

The present study tries to find an answer to the question, whether the consumption of cannabis can cause flashbacks, and, if so, under what circumstances they occur. This is of interest for the treatment, prognosis and also from the legal viewpoint. The definition of a flashback is often unclear. Empirical investigations are often not sufficiently comparable, the supplementary data are very often missing, making the evaluation of the results difficult. Self-diagnosis by the consumer is usually unsuitable for estimating the frequency and phenomenology of flashbacks. Cannabis may trigger flashbacks after consuming hallucinogenes; the probability of the occurrence of a flashback seems to increase with the amount of hallucinogenes a person has consumed. A definite correlation between the amount of hashish consumed and the occurrence of flashback does not exist. Flashbacks have also been reported after consuming cannabis alone. However, data vary regarding the frequency of such flashbacks. According to the available data they occur rarely and require a thorough differential diagnostic evaluation in each individual case. As a rule, the occurrence of a flashback may take place in cases where there is an intake of hallucinogenic drugs in the recent case history.

Frecska, E., & Luna, L. E. (2006). The adverse effects of hallucinogens from intramural perspective Neuropsychopharmacologia Hungarica : A Magyar Pszichofarmakologiai Egyesulet Lapja = Official Journal of the Hungarian Association of Psychopharmacology, 8(4), 189-200.

Very recently, after a long-lasting, worldwide moratorium on research of hallucinogenic agents, a good number of advanced countries have been revising their position, and start to approve testing the physiological and therapeutic effects of hallucinogens in human subjects. The purpose of this article is to review safety information available in the literature on hallucinogen use, and sort out those data from the reported complications of their abuse. Because of prohibitory regulations of the last 35 years, there are difficulties in achieving this kind of evaluation. Our approach has to be broad, and at times retrospective, in contrast to the well-controlled, focused, prospective design of the premarketing trials of legal drugs. The article summarizes the analyses in anticipation of supportive regulatory changes for the use of hallucinogens in well controlled studies and strictly supervised clinical trials. Keywords: adverse effects, ayahuasca, N,N-dimethyltryptamine, hallucinogenic agents, ibogaine, lysergic acid diethylamide, N-methyl-3,4-methylenedioxyamphetamine, psilocybin, therapeutic use.

Fried, P., Watkinson, B., James, D., & Gray, R. (2002). Current and former marijuana use: Preliminary findings of a longitudinal study of effects on IQ in young adults CMAJ : Canadian Medical Association Journal = Journal De l’Association Medicale Canadienne, 166(7), 887-891.

BACKGROUND: Assessing marijuana’s impact on intelligence quotient (IQ) has been hampered by a lack of evaluation of subjects before they begin to use this substance. Using data from a group of young people whom we have been following since birth, we examined IQ scores before, during and after cessation of regular marijuana use to determine any impact of the drug on this measure of cognitive function. METHODS: We determined marijuana use for seventy 17- to 20-year-olds through self-reporting and urinalysis. IQ difference scores were calculated by subtracting each person’s IQ score at 9-12 years (before initiation of drug use) from his or her score at 17-20 years. We then compared the difference in IQ scores of current heavy users (at least 5 joints per week), current light users (less than 5 joints per week), former users (who had not smoked regularly for at least 3 months) and non-users (who never smoked more than once per week and no smoking in the past two weeks). RESULTS: Current marijuana use was significantly correlated (p

Frische, M. (1975). Medical bases of drug problems [Medizinische Grundlagen des Drogenproblems ] Das Offentliche Gesundheitswesen, 37(1 Suppl), 12-17.

Funk, F. (1972). Emergency treatment and technic of detoxification in juvenile drug addicts [Notfallbehandlung und Technik der Entgiftung bei jugendlichen Drogenabhangigen ] Fortschritte Der Medizin, 90(19), 723-725.

Fusar-Poli, P., & Borgwardt, S. (2008). Albert hofmann, the father of LSD (1906-2008) Neuropsychobiology, 58(1), 53-54. doi:10.1159/000157779

Gaillard, M. C., & Borruat, F. X. (2003). Persisting visual hallucinations and illusions in previously drug-addicted patients Klinische Monatsblatter Fur Augenheilkunde, 220(3), 176-178. doi:10.1055/s-2003-38173

BACKGROUND: Tetrahydrocannabinol (cannabis) and lysergic acid diethylamide (LSD) are psychomimetic agents that induce impairment of sensory perception. Illusions and hallucinations are mostly visual. Most frequently the visual phenomena occur in conjunction with drug abuse. PATIENTS AND METHODS: Three previously drug-addicted patients were examined for either persisting or spontaneously recurrent visual phenomena. Two patients complained of persisting visual illusions (vibrations, dyskinetopsia and impaired depth perception) during more than 12 months after an excessive use of cannabis. The third patient was a multiple drug abuser (LSD for 6 years) and complained of visual hallucinations and palinopsia following heavy ethanol intake, 20 years after stopping the use of any drug. RESULTS: Results from neuro-ophthalmic and neurological examinations were normal for the first two patients. The third patient presented abnormal visual fields with preserved visual acuity; electroencephalography was abnormal, suggesting an underlying toxic encephalopathy. CONCLUSIONS: Persistent visual illusions or hallucinations can occur during several months after an intake of cannabis. Flash-back phenomena are frequent amongst LSD abusers. They rarely occur at long times after the last intake (20 years in the present case); when they do so, precipitating factors are often present (ethanol, medication, anesthesia). Such phenomena reflect the cortical dysfunctions that can be induced by illegal substances.

Garcia Lopez, A., & Ezquiaga Terrazas, E. (1988). Neuropsychologic disorders in drug addicts [Trastornos neuropsicologicos en toxicomanos ] Actas Luso-Espanolas De Neurologia, Psiquiatria y Ciencias Afines, 16(6), 425-433.

Geyer, M. A., & Vollenweider, F. X. (2008). Serotonin research: Contributions to understanding psychoses Trends in Pharmacological Sciences, 29(9), 445-453.

The history of serotonin research is closely related to the study of hallucinogenic drugs that function as agonists at serotonin-2A receptors. The fundamental idea that psychotic states seen in psychiatric disorders such as schizophrenia might be attributable, in part, to abnormalities in serotonergic systems began with the almost simultaneous discovery of lysergic acid diethylamide (LSD), psilocybin and serotonin. Sixty years of study have confirmed early speculations regarding the important relationship between serotonin and both drug-induced and disorder-based psychotic states. Now, modern biochemical, pharmacological, behavioral, neuroimaging, genetic and molecular biological sciences are converging to understand how serotonergic systems interact with other monoaminergic and glutamatergic systems to modulate states of consciousness and contribute to psychotic disorders such as the group of schizophrenias. This review summarizes experimental assessments of the serotonergic hallucinogen model psychosis in relation to the serotonin hypothesis of schizophrenia.

Ghuran, A., & Nolan, J. (2000). Recreational drug misuse: Issues for the cardiologist Heart (British Cardiac Society), 83(6), 627-633.

Glennon, R. A., Young, R., Jacyno, J. M., Slusher, M., & Rosecrans, J. A. (1983). DOM-stimulus generalization to LSD and other hallucinogenic indolealkylamines European Journal of Pharmacology, 86(3-4), 453-459.

Stimulus generalization studies were conducted using rats trained to discriminate 1.0 mg/kg of the phenalkylamine hallucinogen 1-(2,5-dimethoxy-4-methylphenyl)-2-aminopropane (DOM) from saline in a two-lever operant procedure. The results suggest that certain indolealkylamine hallucinogens, including LSD and several alpha-methyltryptamine, N,N-dialkyltryptamine and beta-carboline derivatives, are capable of producing stimulus effects similar to those produced by DOM. Furthermore, for twelve agents where human data are available, a significant correlation exists between discrimination-derived ED50 values and hallucinogenic potency.

Gould, L. C., Berberian, R. M., Kasl, S. V., Thompson, W. D., & Kleber, H. D. (1977). Sequential patterns of multiple-drug use among high school students Archives of General Psychiatry, 34(2), 216-222.

Only recently have multiple-drug use studies involving more than heroin and marijuana begun to be reported in the literature. Four of these studies have found evidence that multiple-drug use is a progressive phenomenon, although the particular pattern of multiple-drug use reported in different populations varies somewhat. This study examines the patterns of multiple-drug use reported by a random sample of 1,094 high school students living in greater New Haven, Conn in the 1972-1973 academic school year. Scalogram analysis reveals a progressive relationship for nine drugs: alcohol, marijuana, hashish, barbiturates, amphetamines, LSD, mescaline, cocaine, and heroin. Cigarettes and glue were not found to play a part in this pattern. The temporal order in which respondents reported that they had begun using each drug supports the results of scalogram analysis only in part.

Green, A. R. (2008). Gaddum and LSD: The birth and growth of experimental and clinical neuropharmacology research on 5-HT in the UK British Journal of Pharmacology, 154(8), 1583-1599. doi:10.1038/bjp.2008.207

The vasoconstrictor substance named serotonin was identified as 5-hydroxytryptamine (5-HT) by Maurice Rapport in 1949. In 1951, Rapport gave Gaddum samples of 5-HT substance allowing him to develop a bioassay to both detect and measure the amine. Gaddum and colleagues rapidly identified 5-HT in brain and showed that lysergic acid diethylamide (LSD) antagonized its action in peripheral tissues. Gaddum accordingly postulated that 5-HT might have a role in mood regulation. This review examines the role of UK scientists in the first 20 years following these major discoveries, discussing their role in developing assays for 5-HT in the CNS, identifying the enzymes involved in the synthesis and metabolism of 5-HT and investigating the effect of drugs on brain 5-HT. It reviews studies on the effects of LSD in humans, including Gaddum’s self-administration experiments. It outlines investigations on the role of 5-HT in psychiatric disorders, including studies on the effect of antidepressant drugs on the 5-HT concentration in rodent and human brain, and the attempts to examine 5-HT biochemistry in the brains of patients with depressive illness. It is clear that a rather small group of both preclinical scientists and psychiatrists in the UK made major advances in our understanding of the role of 5-HT in the brain, paving the way for much of the knowledge now taken for granted when discussing ways that 5-HT might be involved in the control of mood and the idea that therapeutic drugs used to alleviate psychiatric illness might alter the function of cerebral 5-HT.

Gresch, P. J., Smith, R. L., Barrett, R. J., & Sanders-Bush, E. (2005). Behavioral tolerance to lysergic acid diethylamide is associated with reduced serotonin-2A receptor signaling in rat cortex Neuropsychopharmacology : Official Publication of the American College of Neuropsychopharmacology, 30(9), 1693-1702. doi:10.1038/sj.npp.1300711

Tolerance is defined as a decrease in responsiveness to a drug after repeated administration. Tolerance to the behavioral effects of hallucinogens occurs in humans and animals. In this study, we used drug discrimination to establish a behavioral model of lysergic acid diethylamide (LSD) tolerance and examined whether tolerance to the stimulus properties of LSD is related to altered serotonin receptor signaling. Rats were trained to discriminate 60 microg/kg LSD from saline in a two-lever drug discrimination paradigm. Two groups of animals were assigned to either chronic saline treatment or chronic LSD treatment. For chronic treatment, rats from each group were injected once per day with either 130 microg/kg LSD or saline for 5 days. Rats were tested for their ability to discriminate either saline or 60 microg/kg LSD, 24 h after the last chronic injection. Rats receiving chronic LSD showed a 44% reduction in LSD lever selection, while rats receiving chronic vehicle showed no change in percent choice on the LSD lever. In another group of rats receiving the identical chronic LSD treatment, LSD-stimulated [35S]GTPgammaS binding, an index of G-protein coupling, was measured in the rat brain by autoradiography. After chronic LSD, a significant reduction in LSD-stimulated [35S]GTPgammaS binding was observed in the medial prefrontal cortex and anterior cingulate cortex. Furthermore, chronic LSD produced a significant reduction in 2,5-dimethoxy-4-iodoamphetamine-stimulated [35S]GTPgammaS binding in medial prefrontal cortex and anterior cingulate cortex, which was blocked by MDL 100907, a selective 5-HT2A receptor antagonist, but not SB206553, a 5-HT2C receptor antagonist, indicating a reduction in 5-HT2A receptor signaling. 125I-LSD binding to 5-HT2A receptors was reduced in cortical regions, demonstrating a reduction in 5-HT2A receptor density. Taken together, these results indicate that adaptive changes in LSD-stimulated serotonin receptor signaling may mediate tolerance to the discriminative stimulus effects of LSD.

Griffiths, R. R., Richards, W. A., McCann, U., & Jesse, R. (2006). Psilocybin can occasion mystical-type experiences having substantial and sustained personal meaning and spiritual significance. Psychopharmacology, 187(3), 268-83; discussion 284-92.

RATIONALE: Although psilocybin has been used for centuries for religious purposes, little is known scientifically about its acute and persisting effects. OBJECTIVES: This double-blind study evaluated the acute and longer-term psychological effects of a high dose of psilocybin relative to a comparison compound administered under comfortable, supportive conditions. MATERIALS AND METHODS: The participants were hallucinogen-naive adults reporting regular participation in religious or spiritual activities. Two or three sessions were conducted at 2-month intervals. Thirty volunteers received orally administered psilocybin (30 mg/70 kg) and methylphenidate hydrochloride (40 mg/70 kg) in counterbalanced order. To obscure the study design, six additional volunteers received methylphenidate in the first two sessions and unblinded psilocybin in a third session. The 8-h sessions were conducted individually. Volunteers were encouraged to close their eyes and direct their attention inward. Study monitors rated volunteers’ behavior during sessions. Volunteers completed questionnaires assessing drug effects and mystical experience immediately after and 2 months after sessions. Community observers rated changes in the volunteer’s attitudes and behavior. RESULTS: Psilocybin produced a range of acute perceptual changes, subjective experiences, and labile moods including anxiety. Psilocybin also increased measures of mystical experience. At 2 months, the volunteers rated the psilocybin experience as having substantial personal meaning and spiritual significance and attributed to the experience sustained positive changes in attitudes and behavior consistent with changes rated by community observers. CONCLUSIONS: When administered under supportive conditions, psilocybin occasioned experiences similar to spontaneously occurring mystical experiences. The ability to occasion such experiences prospectively will allow rigorous scientific investigations of their causes and consequences.

Grossman, T. M. (1978). Post-anesthesia catalepsy in an L.S.D. user Anesthesia Progress, 25(4), 123.

Gupta, S. P., Handa, A., Bindal, M. C., & Singh, P. (1983). QSAR studies on psychotomimetic phenylalkylamines Arzneimittel-Forschung, 33(8), 1089-1090.

Attempts have been made to correlate hyperthermic potencies in rabbits and LSD-like effect in rat of a series of phenylisopropylamines (amphetamines) with physico-chemical parameters. In case of 2,4,5-trisubstituted analogs, hyperthermic potencies are found to be well correlated parabolically with the hydrophobic parameter pi. However, for the same series, the LSD-like effect is found to be related with pi in combination of steric parameter of 4-substituent. It is therefore inferred that hyperthermia in rabbit may be the function only of the hydrophobic character of molecule, but the LSD-like effect is influenced by the steric hindrance of 4-substituent also.

Guttman, H. A. (1972). The first trip: Life crisis and the first experience with hallucinogenic drugs The Journal of Nervous and Mental Disease, 154(6), 453-456.

Haddad, L. M. (1976). Management of hallucinogen abuse American Family Physician, 14(1), 82-87.

Most street hallucinogens contain either LSD or phenycyclidine HCl (PCP). Because the acute phase of LSD and PCP mimic several other drugs and conditions, it is important to exclude these other possibilities. When faced with LSD or PCP, “talking down” usually suffices for the mild case; management becomes more complex should hyperpyrexia, coma, seizures or a hypertensive crisis ensue. Diazepam, not a phenothiazine, is preferred for sedation.

Halpern, J. H., & Pope, H. G.,Jr. (1999). Do hallucinogens cause residual neuropsychological toxicity? Drug and Alcohol Dependence, 53(3), 247-256.

We collected and reviewed studies in which neuropsychological tests were administered to users of LSD or other hallucinogens. Interpretation of the studies is limited by various confounding variables, such as subjects’ premorbid cognitive and personality function and prior use of other substances. At present, the literature tentatively suggests that there are few, if any, long-term neuropsychological deficits attributable to hallucinogen use. To better resolve this issue, however, it will be important to study larger samples of chronic, frequent hallucinogen users who have not often used other types of drugs.

Halpern, J. H., & Pope Jr, H. G. (2003). Hallucinogen persisting perception disorder: What do we know after 50 years? Drug & Alcohol Dependence, 69(2), 109.

‘Flashbacks’ following use of hallucinogenic drugs have been reported for decades; they are recognized in DSM-IV as ‘Hallucinogen Persisting Perception Disorder (Flashbacks)’, or HPPD. We located and analyzed 20 quantitative studies between 1955 and 2001 examining this phenomenon. However, many of these studies were performed before operational criteria for HPPD were published in DSM-III-R, so they are difficult to interpret in the light of current diagnostic criteria. Overall, current knowledge of HPPD remains very limited. In particular (1) the term ‘flashbacks’ is defined in so many ways that it is essentially valueless; (2) most studies provide too little information to judge how many cases could meet DSM-IV criteria for HPPD; and consequently (3) information about risk factors for HPPD, possible etiologic mechanisms, and potential treatment modalities must be interpreted with great caution. At present, HPPD appears to be a genuine but uncommon disorder, sometimes persisting for months or years after hallucinogen use and causing substantial morbidity. It is reported most commonly after illicit LSD use, but less commonly with LSD administered in research or treatment settings, or with use of other types of hallucinogens. There are case reports, but no randomized controlled trials, of successful treatment with neuroleptics, anticonvulsants, benzodiazepines, and clonidine. Although it may be difficult to collect large samples of HPPD cases, further studies are critically needed to augment the meager data presently available regarding the prevalence, etiology, and treatment of HPPD. [Copyright 2003 Elsevier]; Copyright of Drug & Alcohol Dependence is the property of Elsevier Science Publishers B.V. and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder’s express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts)

Halpern, M., & Citron, B. P. (1971). Necrotizing angiitis associated with drug abuse The American Journal of Roentgenology, Radium Therapy, and Nuclear Medicine, 111(4), 663-671.

Hauschild, T. B. (1971). Marijuana Military Medicine, 136(2), 105-109.

Heaton, R. K. (1975). Subject expectancy and environmental factors as determinants of psychedelic flashback experiences The Journal of Nervous and Mental Disease, 161(3), 157-165.

This study assessed the roles of expectancy and autonomic arousal in inducing psychedelic flashbacks under conditions of mild sensory deprivation. Subjects with and without previous flashbacks participated. During the first experimental session, subjects were given a drug which they were told would induce flashbacks, and during the second, a drug which was alleged to induce only autonomic arousal. Ephedrine sulfate (causing autonomic changes) or placebo actually was given in counterbalanced order. Subjects of both groups experienced many more psychedelic sensations when they expected flashbacks. Drug effect was nonsignificant. These findings support the view that flashbacks are not “caused” by psychedelic drugs, but by the tendency of some drug users to mislabel and selectively attend to relevant aspects of naturally occurring altered states of consciousness.

Heekeren, K., Neukirch, A., Daumann, J., Stoll, M., Obradovic, M., Kovar, K. A., et al. (2007). Prepulse inhibition of the startle reflex and its attentional modulation in the human S-ketamine and N,N-dimethyltryptamine (DMT) models of psychosis Journal of Psychopharmacology (Oxford, England), 21(3), 312-320. doi:10.1177/0269881107077734

Patients with schizophrenia exhibit diminished prepulse inhibition (PPI) of the acoustic startle reflex and deficits in the attentional modulation of PPI. Pharmacological challenges with hallucinogens are used as models for psychosis in both humans and animals. Remarkably, in contrast to the findings in schizophrenic patients and in animal hallucinogen models of psychosis, previous studies with healthy volunteers demonstrated increased levels of PPI after administration of low to moderate doses of either the antiglutamatergic hallucinogen ketamine or the serotonergic hallucinogen psilocybin. The aim of the present study was to investigate the influence of moderate and high doses of the serotonergic hallucinogen N,N-dimethyltryptamine (DMT) and the N-methyl-D-aspartate antagonist S-ketamine on PPI and its attentional modulation in humans. Fifteen healthy volunteers were included in a double-blind cross-over study with two doses of DMT and S-ketamine. Effects on PPI and its attentional modulation were investigated. Nine subjects completed both experimental days with the two doses of both drugs. S-ketamine increased PPI in both dosages, whereas DMT had no significant effects on PPI. S-ketamine decreased and DMT tended to decrease startle magnitude. There were no significant effects of either drug on the attentional modulation of PPI. In human experimental hallucinogen psychoses, and even with high, clearly psychotogenic doses of DMT or S-ketamine, healthy subjects failed to exhibit the predicted attenuation of PPI. In contrast, PPI was augmented and the startle magnitude was decreased after S-ketamine. These data point to important differences between human hallucinogen models and both animal hallucinogen models of psychosis and naturally occurring schizophrenia.

Hermle, L., Kovar, K. -., Hewer, W., & Ruchsow, M. (2008). Halluzinogen-induzierte psychische störungen. Fortschritte Der Neurologie, Psychiatrie, 76(6), 334-342.

Objective: The purpose of this article is to provide an overview of the current research on hallucinogen induced psychiatric disorders. In addition to LSD and psilocybin hallucinogens of biologic origin are increasingly used by adolescents and young adults. Methods: Relevant literature and related articles were identified by means of a computerized MEDLINE search including the years 1997-2007. As keywords “hallucinogen induced psychosis”, “hallucinogen induced flashback”, “hallucinogen persisting perception disorder (HPPD)” were used. Finally, 64 journal articles and books out of 103 were included in the review. Results: Acute psychotic syndromes in adolescents are rarely due to intoxications with hallucinogenic drugs. However, clinical relevance of flashback phenomena as post-hallucinogenic psychiatric disorder has to be disputed. Because of the high popularity of biogenic hallucinogens and LSD knowledge of intoxications and resulting psychiatric disorders as well as medical complications and therapeutical approaches are clinically important. Especially intoxications with drugs of herbal origin like tropanalcaloids play an important role in emergency situations. (PsycINFO Database Record © 2009 APA, all rights reserved) (from the journal abstract)

Hoffman, J. A. (1984). LSD flashbacks Archives of General Psychiatry, 41(6), 631-632.

HOLLISTER, L. E. (1964). Chemical psychoses Annual Review of Medicine, 15, 203-214. doi:10.1146/annurev.me.15.020164.001223

Holsten, F. (1974). Flashbacks–late reactions after LSD and cannabis use among 78 drug addicts ["Flashbacks"--senreaksjoner etter bruk av LSD og cannabis hos 78 stoffbrukere ] Tidsskrift for Den Norske Laegeforening : Tidsskrift for Praktisk Medicin, Ny Raekke, 94(30), 2070-2077.

Holsten, F. (1976). Flashbacks. clinical and social significance 1 1/2–4 years after the 1st admission ["Flashbacks". Klinisk og sosial betydning 1 1/2--4 ar etter forste behandlingskontakt ] Tidsskrift for Den Norske Laegeforening : Tidsskrift for Praktisk Medicin, Ny Raekke, 96(15), 875-878.

Horowitz, M. J. (1969). Flashbacks: Recurrent intrusive images after the use of LSD The American Journal of Psychiatry, 126(4), 565-569.

Ikeda, A., Sekiguchi, K., Fujita, K., Yamadera, H., & Koga, Y. (2005). 5-methoxy-N,N-diisopropyltryptamine-induced flashbacks. American Journal of Psychiatry, 162(4), 815-815.

Presents a letter to the editor discussing the case of 5-Methoxy-N,N-Diisopropyltryptamine-induced flashbacks. Mr. A, a 35-year-old Japanese man without a previous psychiatric history, was seen with perceptual disturbances. One month before his evaluation, he had stopped using 5-MeO-DIPT because of a so-called bad trip-anxiety, palpitations, auditory oversensitiveness, and visual distortion- after six or seven times using between 15 mg and 30 mg of 5-MeO-DIPT over 5 months. For public safety, 5-MeO-DIPT is a controlled substance in several countries. However, it is available in many areas, and the patient obtained it through the Internet quite easily. As a result, the abuse of 5-MeO-DIPT may be more widespread than previously thought. Further studies are needed to verify the relationship between 5-MeO-DIPT and hallucinogen-persisting perception disorder and to call public attention to the toxicity of 5-MeO-DIPT. (PsycINFO Database Record © 2008 APA, all rights reserved)

Isbell, H. (1971). Clinical aspects of the various forms of nonmedical use of drugs. II Anesthesia and Analgesia, 50(6), 897-905.

Johnson, D. A. (1981). Drug-induced psychiatric disorders Drugs, 22(1), 57-69.

This article is a review of the principal drug-induced psychiatric symptoms that are likely to be encountered in daily clinical practice as a result of drug abuse, overdoses or side effects of drugs prescribed for treatment. Many categories of medication have the potential to produce psychiatric symptoms, but antitubercular drugs, hypotensive agents and steroids have the highest incidence in clinical practice. Additionally, the problems of alcohol are all too frequently overlooked. The variety and frequency of secondary psychiatric symptoms which may be drug-related emphasise the importance of a careful consideration of all drugs taken by a patient with psychiatric complaints, to determine causal association with symptoms.

Johnson, M. W., Richards, W. A., & Griffiths, R. R. (2008). Human hallucinogen research: Guidelines for safety. Journal of Psychopharmacology, 22(6), 603-620.

There has recently been a renewal of human research with classical hallucinogens (psychedelics). This paper first briefly discusses the unique history of human hallucinogen research, and then reviews the risks of hallucinogen administration and safeguards for minimizing these risks. Although hallucinogens are relatively safe physiologically and are not considered drugs of dependence, their administration involves unique psychological risks. The most likely risk is overwhelming distress during drug action (‘bad trip’), which could lead to potentially dangerous behaviour such as leaving the study site. Less common are prolonged psychoses triggered by hallucinogens. Safeguards against these risks include the exclusion of volunteers with personal or family history of psychotic disorders or other severe psychiatric disorders, establishing trust and rapport between session monitors and volunteer before the session, careful volunteer preparation, a safe physical session environment and interpersonal support from at least two study monitors during the session. Investigators should probe for the relatively rare hallucinogen persisting perception disorder in follow-up contact. Persisting adverse reactions are rare when research is conducted along these guidelines. Incautious research may jeopardize participant safety and future research. However, carefully conducted research may inform the treatment of psychiatric disorders, and may lead to advances in basic science. [ABSTRACT FROM AUTHOR]; Copyright of Journal of Psychopharmacology is the property of Sage Publications, Ltd. and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder’s express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts)

Jurgaitiene, D., & Targamadze, V. (2006). Relations between usage of marihuana and other drugs among teenagers [Marihuanos ir kitu narkotiku vartojimo sasajos tarp paaugliu ] Medicina (Kaunas, Lithuania), 42(10), 843-851.

Some supporters of liberal drug politics in the whole world and in Lithuania try to suggest that usage of marihuana and other cannabis products is harmless and marihuana can even be used for medical purposes. They state that usage of cannabis products does not lead to usage of stronger drugs and so on. Other authors state that regular marihuana use always leads to trying stronger drugs and development of drug addiction. The aim of this study is to examine connection between regular marihuana use and other drugs, to find factors that motivate marihuana users to try other drugs, and to name differences of attitude towards drugs and drug addiction between regular and irregular marihuana users. The research was conducted in six vocational schools of Klaipeda; 912 freshman students (mean age 17.5 years) were surveyed. During the survey, anonymous questionnaires were administered, and data were processed using SPSS program package. During the study, it was established that 15.6% of vocational schools’ males and 4.9% of females smoked marihuana often or more often (more than 20 times). Those students are regular marihuana users, and they already may need medical or psychological help. Behavior and attitude of regular marihuana towards drugs users, which can be named as tolerance towards all drug usage ideology, statistically significantly differed from ideology of irregular marihuana users. The following percentage of regular marihuana users have also tried other illegal drugs: 58.6% have tried psychostimulants in the form of pills or powder (amphetamine, ecstasy, LSD, and others), 20.0% have tried intravenous drugs, 19.2%–various other drugs, and 42.4%–alcohol with pills.

Juve, J. L. (1972). Bad drug trips and flashbacks Child Welfare, 51(1), 41-50.

Kaminer, Y., & Hrecznyj, B. (1991). Lysergic acid diethylamide-induced chronic visual disturbances in an adolescent The Journal of Nervous and Mental Disease, 179(3), 173-174.

Kawasaki, A., & Purvin, V. (1996). Persistent palinopsia following ingestion of lysergic acid diethylamide (LSD) Archives of Ophthalmology, 114(1), 47-50.

OBJECTIVE: To identify a distinctive chronic visual complication of lysergic acid diethylamide (LSD) use. DESIGN: Description of the clinical findings in three patients with this disorder. SETTING: A neuro-ophthalmology referral center. RESULTS: All three patients experienced prolonged afterimages (palinopsia) during LSD intoxication and have continued to be symptomatic up to 3 years after they ceased to ingest the drug. Results of neuro-ophthalmologic and neurologic examinations and neuroimaging and electrophysiologic studies were normal. CONCLUSIONS: We have described three patients in whom persistent palinopsia developed following ingestion of LSD. Clinicians should inquire about past LSD use in all patients who initially have seemingly spontaneous, isolated palinopsia. Recognition of this distinctive clinical syndrome associated with LSD use might avoid unnecessary anxiety and excessive diagnostic tests for patients with this disorder.

Kinrys, G., Wygant, L. E., Pardo, T. B., & Melo, M. (2006). Levetiracetam for treatment-refractory posttraumatic stress disorder The Journal of Clinical Psychiatry, 67(2), 211-214.

OBJECTIVE: To assess the use of levetiracetam, a novel anticonvulsant agent, in the treatment of refractory posttraumatic stress disorder (PTSD). METHOD: Retrospective analysis was conducted of 23 patients with DSM-IV diagnosis of PTSD who, after being deemed partial or nonresponders to antidepressant therapy, received levetiracetam in a naturalistic fashion. The primary outcome measure was the PTSD Checklist-Civilian Version (PCL-C). Secondary outcome measures included the Hamilton Rating Scale for Anxiety (HAM-A), the Hamilton Rating Scale for Depression (HAM-D), Clinical Global Impressions-Severity of Illness scale (CGI-S), and Clinical Global Impressions-Improvement scale (CGI-I). RESULTS: Levetiracetam at a mean+/-SD dose of 1967+/-650 mg/day for 9.7+/-3.7 weeks was generally well tolerated. Nineteen patients (83%) were taking at least 1 concomitant medication. Patients were severely ill with a mean baseline PCL-C score of 67.2+/-9.4, CGI-S score of 6.0+/-0.7, and HAM-A score of 26.8+/-4.9. Patients improved significantly on all measures (p

Kliner, D. J., & Pickens, R. (1982). Indicated preference for drugs of abuse The International Journal of the Addictions, 17(3), 543-547.

Experienced polydrug abusers (N = 190) were asked to indicate previous drugs used as well as drug preferences. The 11 most frequently used drugs were ranked according to percentage of subjects preferring each drug relative to reference compounds (marijuana, alcohol, amphetamine, and cocaine). A highly consistent ranking of drug preference was obtained across reference compounds. The mean ordinal ranking of drug preference was heroin (highest), amphetamine, alcohol, pentobarbital, secobarbital, marijuana, cocaine, codeine, diazepam, LSD, and hashish (lowest). The ranking of drugs by preference was unrelated to incidence of use of drug accessibility.

Kornblith, A. B. (1981). Multiple drug abuse involving nonopiate, nonalcoholic substances. II. physical damage, long-term psychological effects and treatment approaches and success The International Journal of the Addictions, 16(3), 527-540.

A review of the literature of multiple drug abuse involving two or more drug categories where at least one is a nonopiate, nonalcoholic substance (MDA NONA) suggested the possibility that sedative-hypnotics were the culpable agent for neuropsychological deficits in this group. Individually, amphetamines and hallucinogens, primarily LSD, have been associated with long-term psychological disturbance. While many abusers of these drugs who develop psychoses have been documented to be emotionally disturbed prior to drug usage, indicating that the drug exacerbated a prepsychotic condition, other abusers have no such history, indicating a drug-induced psychosis. Current treatment approaches appear to be ineffective for MDA-NONA abusers, as indicated by poor retention rates and relapse to drug use.

Kozaric-Kovacic, D., Pivac, N., Muck-Seler, D., & Rothbaum, B. O. (2005). Risperidone in psychotic combat-related posttraumatic stress disorder: An open trial The Journal of Clinical Psychiatry, 66(7), 922-927.

RATIONALE: Psychotic symptoms that frequently occur in combat-related posttraumatic stress disorder (PTSD) complicate its pharmacotherapy. We hypothesized that war veterans with psychotic PTSD, resistant to prior antidepressant treatment, would respond well to 6 weeks of treatment with the atypical antipsychotic risperidone, given as a monotherapy. METHOD: Twenty-six male war veterans with psychotic PTSD (DSM-IV) completed the 6-week inpatient treatment with risperidone (2-4 mg/day) during the period from November 1999 through December 2002. The primary outcome measure was change from baseline to endpoint (6 weeks) in Positive and Negative Syndrome Scale (PANSS) total and subscale scores. Secondary outcome measures were changes in PTSD Interview (PTSD-I) and Clinical Global Impressions-Severity of Illness scale (CGI-S) total and subscale scores. Clinical improvement was assessed by CGI-S, CGI-Improvement scale, and Patient Global Impression of Improvement scale, while adverse events were recorded by Drug-Induced Extrapyramidal Symptoms Scale. RESULTS: Treatment with risperidone for either 3 or 6 weeks in an open trial significantly reduced total and subscales scores on the PANSS and on the PTSD-I and CGI-S when compared to baseline scores in patients with psychotic PTSD. CONCLUSION: Our preliminary data from the open trial indicate that risperidone decreased most of the psychotic and PTSD symptoms. Psychotic PTSD patients, unresponsive to antidepressant treatment, improved significantly after treatment for either 3 or 6 weeks with risperidone.

Kuehnle, J., Mendelson, J. H., Davis, K. R., & New, P. F. (1977). Computed tomographic examination of heavy marijuana smokers JAMA : The Journal of the American Medical Association, 237(12), 1231-1232.

Computed tomographic scans were obtained from 19 men with long histories of heavy marijuana smoking and who were also observed to smoke large amounts of marijuana under research ward conditions. The ventricular system and subarachnoid spaces were normal in size and showed no indication of atrophic change.

Landabaso, M. A., Iraurgi, I., Jimenez-Lerma, J. M., Calle, R., Sanz, J., & Gutierrez-Fraile, M. (2002). Ecstasy-induced psychotic disorder: Six-month follow-up study European Addiction Research, 8(3), 133-140.

OBJECTIVE: To describe the psychiatric symptoms manifested by persons diagnosed for the first time as having ecstasy-induced psychotic disorder and to explore the evolution of their symptoms over a 6-month period. DESIGN: Observational study with a 6-month follow-up. METHOD: The subjects studied were 32 ecstasy consumers who were treated at two drug-dependency outpatient centers for hallucinatory-delusive manifestations and who were diagnosed as having ecstasy-induced psychotic disorder according to DSM-IV criteria. For the assessment of the intensity of the syndrome and its follow-up, the Brief Psychiatric Rating Scale (BPRS), the Hamilton Depression Rating Scale (HDRS) and the Clinical Global Impression (CGI) were used at the outset and after 1, 3 and 6 months. All subjects received treatment with olanzapine. RESULTS: The treatment program was completed by 96.9% of the patients. At the baseline assessment, a high incidence of symptoms of a severe psychiatric disorder was observed. From the first month the psychotic symptoms (BPRS) were considerably reduced with treatment, with the most severe positive symptoms remitting in the first 3 months. The three assessment indicators (BPRS, HDRS and CGI) showed a statistically significant clinical reduction over the 6 months of the assessment period. Furthermore, no relevant side effects were noted. CONCLUSIONS: In its initial manifestations, a drug-induced psychotic syndrome includes marked symptoms meeting the criteria of a severe psychotic disorder, with the presence of considerable positive and negative symptoms. Olanzapine has been shown to be very effective in these situations and its use is suggested as first-choice therapy.

Lauterbach, E. C., Abdelhamid, A., & Annandale, J. B. (2000). Posthallucinogen-like visual illusions (palinopsia) with risperidone in a patient without previous hallucinogen exposure: Possible relation to serotonin 5HT2a receptor blockade. Pharmacopsychiatry, 33(1), 38-41.

Previous reports document visual illusions resembling hallucinogen persisting perception disorder (HPPD) after risperidone treatment in patients with histories of previous LSD exposure. The authors report the case of a 55-yr-old White female with a 16-yr history of bipolar disorder who suffered visual disturbances resembling HPPD after each of three consecutive risperidone dose increases. The patient lacked any history of substance abuse, particularly hallucinogen exposure. She lacked neurologic or other contributory illnesses. Illusions generally remitted within 48 hrs each time. Coadministration of trazodone and clonazepam may have contributed to these phenomena, although clonazepam has been used to treat this condition. She had been unusually sensitive to the side-effects of many psychotropics. This case is unique due to the absence of substance abuse. This and another report note heightened sensitivity to medication side-effects. Visual phenomena resembling HPPD evidently can occur with risperidone and, possibly, other atypical antipsychotics and certain antidepressants regardless of previous hallucinogen use. Several lines of evidence implicate reduced 5HT2a serotonin (5-hydroxytryptamine [5-HT]) receptor stimulation rather than increased 5HT2c stimulation. (PsycINFO Database Record © 2008 APA, all rights reserved)

Lerner, A. G., Gelkopf, M., Oyffe, I., Finkel, B., Katz, S., Sigal, M., et al. (2000). LSD-induced hallucinogen persisting perception disorder treatment with clonidine: An open pilot study. International Clinical Psychopharmacology, 15(1), 35-37.

A pilot open study was conducted in order to evaluate the efficacy of clonidine in the treatment of LSD-induced hallucinogen persisting perception disorder (HPPD). Eight patients (aged 21-26)fulfilled entrance criteria. All complained of HPPD for at least 3 mo and were drug free at least 3 mo. They received fixed low doses of clonidine, 0.025 mg, 3 times a day for 2 mo. They were evaluated by the Clinical Global Impression Scale (CGI) and a self-report scale on the severity of symptoms. One patient dropped out at wk 3 and a second patient dropped out at wk 5. Of the 6 patients remaining at the end of 2 mo, the average CGI score was 2.5 and the self-report scale score was 2, indicating mild symptomatology. LSD-related flashbacks associated with excessive sympathetic nervous activity may be alleviated with clonidine in some patients. (PsycINFO Database Record © 2008 APA, all rights reserved)

Lerner, A. G., Shufman, E., Kodesh, A., Rudinski, D., Kretzmer, G., & Sigal, M. (2002). Risperidone-associated, benign transient visual disturbances in schizophrenic patients with a past history of LSD abuse The Israel Journal of Psychiatry and Related Sciences, 39(1), 57-60.

Two schizophrenic patients, who had a prior history of LSD abuse and who had previously developed EPS with classic antipsychotics, were successfully treated with risperidone. They both reported short episodes of transient visual disturbances, which appeared immediately after starting treatment with risperidone. This imagery resembled visual disturbances previously experienced as “flashbacks” related to prior LSD consumption. Risperidone administration was continued and the visual disturbances gradually wore off. During a six-month follow-up period, there was no recurrence of visual disturbances. This phenomenon may be interpreted as a benign, short-term and self-limiting side effect which does not contraindicate the use of risperidone or interfere with treatment. Conclusions based on two case reports should be taken with appropriate caution.

Lerner, A. G., Finkel, B., Oyffe, I., Merenzon, I., & Sigal, M. (1998). Clonidine treatment for hallucinogen persisting perception disorder. American Journal of Psychiatry, 155(10), 1460-1460.

Reports the case of treatment for a 25-yr-old man with a history of substance abuse who met Diagnostic and Statistical Manual of Mental Disorders-IV (DSM-IV) criteria for hallucinogen persisting perception disorder. The S was treated with clonidine 3 times per day. Over the next 2 mo, symptoms disappeared completely, and clonidine was discontinued. The S remained symptom free over a 6-mo follow-up period. (PsycINFO Database Record © 2008 APA, all rights reserved)

Lerner, A. G., Gelkopf, M., Skladman, I., Oyffe, I., Finkel, B., Sigal, M., et al. (2002). Flashback and hallucinogen persisting perception disorder: Clinical aspects and pharmacological treatment approach. Israel Journal of Psychiatry and Related Sciences, 39(2), 92-99.

One unique characteristic of LSD and LSD-like substances is the recurrence of some of the symptoms which appeared during the intoxication after the immediate effect of the hallucinogen has worn off. This recurring syndrome, mainly visual, has not been clearly understood, appreciated or distinguished from other clinical entities by clinicians. The terms Flashback and Hallucinogen Persisting Perception Disorder (HPPD) are used interchangeably in the professional literature. Flashback is a usually short-term, non-distressing, spontaneous, recurrent, reversible and benign condition accompanied by a pleasant affect. In contrast, HPPD is a generally long-term, distressing, spontaneous, recurrent, pervasive, either slowly reversible or irreversible, non-benign condition accompanied by an unpleasant dysphoric affect. Flashback and HPPD appear to be part of a vast and broad spectrum of non-psychopathological and psychopathological states reported by hallucinogen users. Pharmacological agents such as clonidine, perphenazine and clonazepam have been shown to ameliorate this syndrome in some of the individuals seeking treatment. (PsycINFO Database Record © 2008 APA, all rights reserved)

Lerner, A. G., Gelkopf, M., Skladman, I., Rudinski, D., Nachshon, H., & Bleich, A. (2003). Clonazepam treatment of lysergic acid diethylamide-induced hallucinogen persisting perception disorder with anxiety features. International Clinical Psychopharmacology, 18(2), 101-105.

A characteristic of lysergic acid diethylamide (LSD) and LSD-like substances is the recurrence of some of the symptoms which appear during the intoxication, in the absence of recent intake of hallucinogens. Hallucinogen persisting perception disorder (HPPD) is a condition in which the re-experiencing of 1 or more perceptual symptoms causes significant distress or impairment in social, occupational or other important areas of functioning and may be extremely debilitating. Benzodiazepines are one of the recommended agents for the treatment of HPPD but it is unclear which of them may be more helpful. Our investigation assessed the efficacy of clonazepam in the treatment of LSD-induced HPPD. 16 Ss participated. All complained of HPPD with anxiety features for at least 3 mo and were drug free at least 3 mo. They received clonazepam 2 mg/day for 2 mo. Follow-up (FO) was continued for 6 mo. They were weekly evaluated during the 2 mo of clonazepam administration and monthly during the FO period using the Clinical Global Impression Scale, a Self-report Scale and Hamilton Anxiety Rating Scale. Ss reported a significant relief and the presence of only mild symptomatology during the clonazepam administration. This improvement was clearly sustained and persisted during a 6-mo FO period. (PsycINFO Database Record © 2008 APA, all rights reserved)

Lerner, A. G., Oyffe, I., Isaacs, G., & Sigal, M. (1997). Naltrexone treatment of hallucinogen persisting perception disorder. American Journal of Psychiatry, 154(3), 437-437.

Presents a report of 2 patients (22 and 24 yr old males with histories of LSD abuse) with hallucinogen persisting perception disorder who were successfully treated with naltrexone (NLX), a long-acting, orally administered opioid antagonist. NLX appears to be useful in some patients who suffer from flashbacks. One of the proposed mechanisms of NLX’s efficacy is that hallucinogen-induced flashbacks may be so distressing as to represent painful stimuli, which have been shown to provoke a greater release of endorphins. (PsycINFO Database Record © 2008 APA, all rights reserved)

Lerner, A. G., Shufman, E., Kodesh, A., Kretzmer, G., & Sigal, M. (2002). LSD-induced hallucinogen persisting perception disorder with depressive features treated with reboxetine: Case report. Israel Journal of Psychiatry and Related Sciences, 39(2), 100-103.

Presents the case of a male 26-yr-old patient who had a prior history of cannabis, ecstasy (MDMA) and LSD abuse and who developed both Hallucinogen Persisting Perception Disorder and a major depressive episode. Following 2 unsuccessful trials with serotonin reuptake inhibitors, reboxetine was prescribed. During a 6-mo follow-up period on reboxetine 6 mg/day, no exacerbation of the visual disturbance or recurrence of the depressive features were reported. Reboxetine may have an ?-sub-2 adrenoreceptor modulating effect on both noradrenaline and serotonin release, thus reboxetine’s ?-sub-2 adrenoreceptor modulating effect on noradrenaline release may affect sympathetic activity and be involved in the recovery process. (PsycINFO Database Record © 2008 APA, all rights reserved)

Lerner, A. G., Skladman, I., Kodesh, A., Sigal, M., & Shufman, E. (2001). LSD-induced hallucinogen persisting perception disorder treated with clonazepam: Two case reports. Israel Journal of Psychiatry and Related Sciences, 38(2), 133-136.

Notes that benzodiazapines are recommended for the treatment of Hallucinogen Persisting Perception Disorder (HPPD), although it is unclear which may be more helpful. Two out-patients (24-yr-old and 22-yr-old males) with LSD-induced HPPD were successfully treated with clonazepam. They had not responded to low potency benzodiazepines or low doses of classic antipsychotics. After clonazepam discontinuation they reported a marked improvement and only mild symptomatology which persisted during a 6 mo follow-up period. High potency benzodiazepines like clonazepam, which has serotonergic properties, may be superior to low-potency benzodiazepines in the treatment of some patients with LSD-induced HPPD. (PsycINFO Database Record © 2008 APA, all rights reserved)

Lerner, V., Bergman, J., Statsenko, N., & Miodownik, C. (2004). Vitamin B6 treatment in acute neuroleptic-induced akathisia: A randomized, double-blind, placebo-controlled study The Journal of Clinical Psychiatry, 65(11), 1550-1554.

BACKGROUND: Treatment strategies for acute neuroleptic-induced akathisia (NIA) contain anticholinergic (antimuscarinic) agents, dopamine agonists, gamma-aminobutyric acid (GABA)-ergic agents, beta-blockers, benzodiazepines, and serotonin antagonists. Nevertheless, many patients who suffer from acute akathisia fail to respond to treatment. In earlier studies, vitamin B6 was found to be effective in the treatment of neuroleptic-induced movement disorders. The purpose of this study was to evaluate the efficacy of vitamin B6 in the treatment of acute NIA. This is the first report of B6 as a treatment for NIA. METHOD: This study was conducted in 2 mental health centers from February 2003 to November 2003. Twenty schizophrenia and schizoaffective inpatients with a DSM-IV diagnosis of NIA were randomly divided to receive vitamin B6 600 mg/day b.i.d. (N = 10) or placebo (N = 10) twice a day for 5 days in a double-blind design. The Barnes Akathisia Scale (BAS), the Brief Psychiatric Rating Scale (BPRS), and the Clinical Global Impressions scale (CGI) were used to assess the severity of NIA and psychotic symptoms. The BAS assessment was made at baseline and every day during the study. The BPRS and CGI were completed at baseline and at the end of the study. RESULTS: The vitamin B6-treated patients in comparison with the placebo group showed a significant improvement on the subjective-awareness of restlessness (p = .0004), subjective-distress (p = .01), and global (p = .004) subscales of the BAS. The objective subscale did not demonstrate significant positive results (p = .079), but there was a trend of symptom amelioration in the vitamin B6 group. A reduction of at least 2 points on the BAS global subscale was noted in 8 patients in the vitamin B6 group (80%), and in only 3 patients in the placebo group (30%) (p = .037). CONCLUSION: Our preliminary results indicate that high doses of vitamin B6 may be useful additions to the available treatments for NIA, perhaps due to its combined effects on various neurotransmitter systems.

Letter: Marijuana flashbacks (1973). The American Journal of Psychiatry, 130(12), 1399-1400.

Li, J. H., & Lin, L. F. (1998). Genetic toxicology of abused drugs: A brief review Mutagenesis, 13(6), 557-565.

Although numerous studies have been conducted on abused drugs, most focus on the problems of addiction (dependence) and their neurotoxicities. Now accumulated data have demonstrated that the genotoxicity and/or carcinogenicity of abused drugs can also be detrimental to our health. In this review, commonly abused substances, including LSD, opiates (diacetylmorphine, morphine, opium and codeine), cocaine, cannabis, betel quid and khat, are discussed for their potential genotoxicity/carcinogenicity. The available literature in the field, although not as abundant as for neurotoxicity, clearly indicates the capability of abused drugs to induce genotoxicity.

Louria, D. B. (1969). Medical complications of pleasure-giving drugs Archives of Internal Medicine, 123(1), 82-87.

Lsd (1967). The Medical Letter on Drugs and Therapeutics, 9(1), 1-2.

Mack, R. B. (1985). Aquarius redux–lysergic acid diethylamide North Carolina Medical Journal, 46(6), 343-344.

Madden, J. S. (1994). LSD and post-hallucinogen perceptual disorder Addiction (Abingdon, England), 89(6), 762-763.

Malitz, S., & Kanzler, M. (1970). Effects of drugs on perception in man Research Publications – Association for Research in Nervous and Mental Disease, 48, 35-53.

Markel, H., Lee, A., Holmes, R. D., & Domino, E. F. (1994). LSD flashback syndrome exacerbated by selective serotonin reuptake inhibitor antidepressants in adolescents The Journal of Pediatrics, 125(5 Pt 1), 817-819.

Two adolescents with a long history of abuse of lysergic acid diethylamide (LSD) and symptoms consistent with major depressive disorder, on initiation of antidepressant therapy with selective serotonin reuptake inhibitor agents, had the new onset or worsening of LSD flashback syndrome. The similarity in neuroreceptor physiology for both LSD and serotonin suggests that the LSD flashback syndrome may be induced by these drugs in patients with a history of LSD abuse.

Marrazzi, A. S., Meisch, R. A., Pew, W. L., & Bieter, T. G. (1966). Quantified LSD effects on ego strength Recent Advances in Biological Psychiatry, 9, 197-207.

Matefy, R. E., Hayes, C., & Hirsch, J. (1978). Psychedelic drug flashbacks: Subjective reports and biographical data Addictive Behaviors, 3(3-4), 165-178.

Matefy, R. E. (1973). Behavior therapy to extinguish spontaneous recurrences of LSD effects: A case study. Journal of Nervous and Mental Disease, 156(4), 226-231.

Describes the application of systematic desensitization in conjunction with other behavior techniques to treat a client who for 5 mo was experiencing spontaneous recurrences of LSD effects. Besides the elimination of the target symptoms (flashback effects), additional desired changes occurred on both cognitive-affective and behavioral levels. A theoretical explanation of LSD flashback effects based on the role-enactment model is presented. (16 ref.) (PsycINFO Database Record © 2008 APA, all rights reserved)

McGennis, A. (1979). Psychiatric symptoms and hallucinogenic compounds British Medical Journal, 2(6193), 797.

McKenna, D. J., & Saavedra, J. M. (1987). Autoradiography of LSD and 2,5-dimethoxyphenylisopropylamine psychotomimetics demonstrates regional, specific cross-displacement in the rat brain European Journal of Pharmacology, 142(2), 313-315.

Menza, M., Lauritano, M., Allen, L., Warman, M., Ostella, F., Hamer, R. M., et al. (2001). Treatment of somatization disorder with nefazodone: A prospective, open-label study Annals of Clinical Psychiatry : Official Journal of the American Academy of Clinical Psychiatrists, 13(3), 153-158.

Somatization disorder (SD) is commonly seen in medical clinics and is associated with significant impairment in functioning as well as excessive utilization of health care. While antidepressants have been studied in some functional somatic syndromes such as fibromyalgia and chronic fatigue, there are no pharmacologic treatment studies of SD itself. In this prospective, 8-week, open-label study, 15 patients diagnosed with either full SD or abridged somatization, by Escobar’s criteria (four unexplained physical symptoms for men or six for women), were given nefazodone, titrated to 150 mg bid. The primary outcomes included measures of physical symptom severity (visual analogue scale), functioning (SF-36), and overall improvement (CGI). Fourteen of the 15 patients achieved the target dose of 300 mg/day and completed the trial. 73% of the patients were rated as improved on the CGI, 79% improved on the self-rated visual analogue scale and 73% of the patients improved on the SF-36. There was significant improvement for the whole group (prepost) on the SF-36, as well as on the HAM-D and the HAM-A. Of the nine patients with a categorical depression diagnosis, 55% of them were rated as improved on the CGI, and 67% improved on both the VAS and the SF-36. Of the six nondepressed patients, 67% were rated as improved on the CGI, 83% improved on the SF-36, and 50% improved on the VAS. Adverse events were generally mild and resulted in only one discontinuation. Although these data need to be confirmed in a larger, double-blind, placebo-controlled trial, they suggest that patients with SD will accept and tolerate therapy with nefazodone and that nefazodone may be a useful treatment for these patients.

Milman, D. H., & Anker, J. L. (1971). Patterns of drug usage among university students. IV. use of marihuana, amphetamines, opium, and LSD by undergraduates Journal of the American College Health Association, 20(2), 96-105.

Mohr, E., Mendis, T., Hildebrand, K., & De Deyn, P. P. (2000). Risperidone in the treatment of dopamine-induced psychosis in parkinson’s disease: An open pilot trial Movement Disorders : Official Journal of the Movement Disorder Society, 15(6), 1230-1237.

PURPOSE: To evaluate the safety and efficacy of risperidone in patients with Parkinson’s disease (PD) who are experiencing significant dopamine-induced psychosis. PATIENTS AND METHODS: Seventeen patients (median age, 72 yrs) participated in this 12-week, open pilot study receiving 0.5 to 3 mg oral risperidone per day. Maintenance antiparkinsonian medication was continued throughout, although psychotropic medication was discontinued. EFFICACY RESULTS: Risperidone produced a substantial improvement in psychotic symptoms, shown on the mean total positive subscale score on the Positive and Negative Syndrome Scale (PANSS) by a 30% improvement (-3.1 decrease) after 1 week and a 66% improvement (-6.8 decrease) at end point. This improvement was most evident in the items delusions, hallucinatory behavior, and suspiciousness/persecution. Risperidone also achieved significant improvement from baseline in Clinical Global Impression (CGI)-severity and CGI-improvement (p

Mokler, D. J., Commissaris, R. L., Warner, M. R., & Rech, R. H. (1983). Blockade of the behavioral effects of lysergic acid diethylamide, 2,5-dimethoxy-4-methylamphetamine, quipazine and lisuride by 5-hydroxytryptamine antagonists The Journal of Pharmacology and Experimental Therapeutics, 227(3), 557-562.

The effects of lysergic acid diethylamide (LSD), 2,5-dimethoxy-4-methylamphetamine (DOM), quipazine or lisuride alone and in combination with the 5-hydroxytryptamine antagonist metergoline, pizotifen and cinanserin were studied in rats responding on a fixed-ratio 40 schedule of food presentation. LSD, DOM, quipazine or lisuride produced a similar dose-dependent decrease in the number of food presentations (ED50 values: 81 micrograms/kg, 0.6 mg/kg, 1.6 mg/kg and 31 micrograms/kg, respectively) and a reciprocal increase in the number of pause intervals (IRTs = 10 sec). All three antagonists attenuated the behavioral effects of LSD and DOM for both food presentations and pause intervals. The LSD-response curve for reinforcers was shifted to the greatest degree by pizotifen (1.0 mg/kg), followed by cinanserin (20 mg/kg) and metergoline (1.0 mg/kg). The ED50 values for this effect were 334, 181 and 141 micrograms/kg, respectively. The DOM dose-response pattern for decrease in reinforcers was shifted to the greatest degree by metergoline, followed by pizotifen and cinanserin (ED50 values: 26.5, 3.2 and 1.8 mg/kg, respectively). The effect of quipazine on reinforcers was antagonized by metergoline and pizotifen (ED50 values: greater than 8.0 for both) but not by cinanserin, although all three antagonists attenuated the increase in pause intervals in the same order as they did for DOM. The decrease in reinforcers by lisuride was equally antagonized by metergoline and pizotifen (ED50 values: 58 and 57 micrograms/kg, respectively), whereas cinanserin potentiated the effect of lisuride (ED50: 16 micrograms/kg).(ABSTRACT TRUNCATED AT 250 WORDS)

Morehead, D. B., & Morehead, D. B. (1997). Exacerbation of hallucinogen-persisting perception disorder with risperidone. US: Lippincott Williams & Wilkins.

A case report is presented which closely resembles those reported by H. D. Abraham and A. Mamen (see record 84-01797) in which risperidone may have exacerbated hallucinogen-persisting perception disorder. A 21-yr-old female with a history of attention deficit hyperactivity disorder (ADHD), polysubstance abuse, and marijuana dependence experienced the onset of severe anxiety symptoms during her 10th lysergic acid diethylamide trip. One to 2 days after starting treatment of risperidone, she related a sharp increase in feelings of generalized anxiety, visual distortions, and panic attacks, which could not be attributed to any other factors. (PsycINFO Database Record © 2008 APA, all rights reserved)

Moskowitz, D. (1971). Use of haloperidol to reduce LSD flashbacks. Military Medicine, 136(9), 754-756.

8 patients who had unpleasant lsd flashbacks were used to study the effects of haloperidol in reducing the frequency of these experiences. There was an increase in the number of flashbacks in the 1st wk. But these decreased over the next 3 wk. For 75% of the ss, flashbacks decreased significantly at the end of the 1-mo period but did not change for the other 2 ss. When haloperidol was discontinued in 3 of the ss, the number of flashbacks increased again. Each of the 8 ss had cns reactions to the drug, which was treated with trihexyphenidyl hc1 to counteract extrapyramidal symptoms. (PsycINFO Database Record © 2008 APA, all rights reserved)

Naditch, M. P. (1975). Ego functioning and acute adverse reactions to psychoactive drugs Journal of Personality, 43(2), 305-320.

The relationship between ego functioning and acute adverse reactions to psychoactive drugs was examined using retrospective data. The data were consistent with a causal model in which characteristic use of regression (and to a lesser extent repression) was associated with acute adverse reactions to marijuana and to LSD. Regression also had an indirect effect through increased usage of LSD. Subjects characterized by the use of intellectualization and denial were less likely to report developing acute adverse reactions. A higher score on a general measure of coping was related to avoiding acute adverse reactions to LSD, but not to marijuana. Projection, regression in the service of the ego, and tolerance of ambiguity has no effect on acute adverse reactions.

Naditch, M. P., Alker, P. C., & Joffe, P. (1975). Individual differences and setting as determinants of acute adverse reactions to psychoactive drugs The Journal of Nervous and Mental Disease, 161(5), 326-335.

The relationship between setting and individual differences in determining acute adverse reactions to psychoactive drugs was examined using retrospective data from 483 drug users. Five dimensions of setting were identified. Although there were some small setting main effects, these effects failed to reach significance when shared variance with individual difference variables was considered. For acute adverse reactions to LSD, however, there were seven independent interaction effects between setting and individual difference variables. There were two interaction effects of smaller magnitude related to acute adverse reactions to marijuana. The significance of these results for the current controversy over the relative importance of situational vs. personality determinants of behavior was discussed.

Naditch, M. P., & Fenwick, S. (1977). LSD flashbacks and ego functioning. Journal of Abnormal Psychology, 86(4), 352-359.

Among 235 male LSD users (mean age 21.2 yrs), Ss experiencing flashbacks (a) were more likely to employ repression and regression, (B) were less likely to use intellectualization, © had less coping capacity and less tolerance of ambiguity, (d) had a more external locus of control, (e) evidenced more thought disorder, (f) were more maladjusted, (g) differed in motives for drug use, (h) used LSD more often, and (i) were more likely to have experienced acute adverse reactions while taking LSD than those Ss who did not have flashbacks. A large battery of tests, including measures of flashbacks; extent of, and motives for, drug use; acute adverse reactions to LSD use; schizophrenia; and regression, denial, coping capacity, and tolerance of ambiguity, was administered to all Ss. Multivariate analysis indicated that, with the exception of repression, differences in ego functioning did not make independent contributions to the variance in flashbacks when shared variance with acute adverse reactions was considered. Several alternative causal interpretations focusing on the significance of acute adverse reactions in the etiology of later flashbacks are discussed. (27 ref) (PsycINFO Database Record © 2008 APA, all rights reserved)

Nagamatsu, K., Kido, Y., & Urakabo, G. (1977). Studies on radioimmunoassay for 2,5-dimethoxy-4-methylamphetamine Chemical & Pharmaceutical Bulletin, 25(12), 3390-3394.

Nassar, N. T., Melikian, L. H., & Der-Karabetian, A. (1973). Studies in the non medical use of drugs in lebanon. I. the non medical use of marijuana, LSD, and amphetamine by students at the american university of beirut Le Journal Medical Libanais.the Lebanese Medical Journal, 26(3), 215-232.

National Institute of, M. H., Lerner, A. G., Gelkopf, M., Oyffe, I., Finkel, B., Katz, S., et al. (2000). Clinical global impression. International Clinical Psychopharmacology, 15, 35-37.

Clinical Global Impression– is a translated/adapted version of the National Institute of Mental Health (1987) measure

Newsletter for research in mental health and behavioral sciences, volume XVI, number 4 No. A/IB-15-51174)Veterans Administration Central Office Library.

Some perspectives on the post-Vietnam syndrome, an article on employee-patient attitude changes and the reorganization of hospital admissions, and reflections on drug abusing patients are included in this issue. Orienting new admissions and dropouts from a day hospital program, changes in self-rated distress and personality traits in alcoholic patients after treatment, and the effects of chronic phenothiazine treatment on adrenal-pituitary function in man are discussed. Also included in this issue is an article on diphenylhydantoin in the treatment of LSD flashbacks. Support for an activation-regulation deficit in schizophrenia and state-trait distinctions in the prediction of the therapeutic efficiency of electroconvulsive shock are discussed. An annotated bibliography on community psychology, recently initiated and recently completed studies are also included.

O’Shea, B., & Fagan, J. (2001). Lysergic acid diethylamide Irish Medical Journal, 94(7), 217.

Osmond, H. (1973). The medical and scientific importance of hallucinogens The Practitioner, 210(255), 112-119.

Oulis, P., Karapoulios, E., Masdrakis, V. G., Kouzoupis, A. V., Karakatsanis, N. A., Papageorgiou, C., et al. (2008). Levetiracetam in the treatment of antipsychotics-resistant tourette syndrome The World Journal of Biological Psychiatry : The Official Journal of the World Federation of Societies of Biological Psychiatry, 9(1), 76-77. doi:10.1080/15622970701233454

Levetiracetam, an anti-epileptic agent that enhances GABAergic neurotransmission, is one of the newest alternative treatments of Tourette syndrome (TS). We present the case of a 23-year-old female patient suffering from TS since the age of 7, who exhibited poor response to a variety of agents (haloperidol, pimozide, clonidine and various adjunctive agents) and had four hospitalizations during the previous 2 years due to the deterioration of her clinical state. On her last admission, in addition to clonidine 600 microg/day (already part of her regimen for the previous 4 years), levetiracetam was prescribed, up to 2000 mg/day, progressively titrated over a 3-week period. The patient presented a significant improvement on her TS symptomatology (the score on the Yale Global Tic Severity Scale dropped from 70 at admission, to 25 five weeks later, at discharge), which was preserved during the subsequent 4 months, without any serious side-effect.

Palenzona, C. (1968). Hallucinogens. medical and social aspects [Gli allucinogeni. Gli aspetti medici e sociali ] Minerva Medica, 59(46 Suppl), 15-17.

Passie, T., Halpern, J. H., Stichtenoth, D. O., Emrich, H. M., & Hintzen, A. (2008). The pharmacology of lysergic acid diethylamide: A review. CNS: Neuroscience & Therapeutics, 14(4), 295-314.

Lysergic acid diethylamide (LSD) was synthesized in 1938 and its psychoactive effects discovered in 1943. It was used during the 1950s and 1960s as an experimental drug in psychiatric research for producing so-called “experimental psychosis” by altering neurotransmitter system and in psychotherapeutic procedures (“psycholytic” and “psychedelic” therapy). From the mid 1960s, it became an illegal drug of abuse with widespread use that continues today. With the entry of new methods of research and better study oversight, scientific interest in LSD has resumed for brain research and experimental treatments. Due to the lack of any comprehensive review since the 1950s and the widely dispersed experimental literature, the present review focuses on all aspects of the pharmacology and psychopharmacology of LSD. A thorough search of the experimental literature regarding the pharmacology of LSD was performed and the extracted results are given in this review. (Psycho-) pharmacological research on LSD was extensive and produced nearly 10,000 scientific papers. The pharmacology of LSD is complex and its mechanisms of action are still not completely understood. LSD is physiologically well tolerated and psychological reactions can be controlled in a medically supervised setting, but complications may easily result from uncontrolled use by layman. Actually there is new interest in LSD as an experimental tool for elucidating neural mechanisms of (states of) consciousness and there are recently discovered treatment options with LSD in cluster headache and with the terminally ill. (PsycINFO Database Record © 2009 APA, all rights reserved) (from the journal abstract)

Passie, T., Schneider, U., & Emrich, H. M. (2002). Persisting continuous visual perception disorder in a chronic MDMA (‘ecstacy’) user. Australian and New Zealand Journal of Psychiatry, 36(2), 266-267.

Presents the case of a 22-yr-old male with a 3-yr history of drug abuse that included cannabis, 3,4-Methylenedioxymethamphetamine (MDMA), and LSD. The S reported a visual perception disorder that did not subside with detoxification. It is hypothesized that the neuropathological basis of this S’s visual aberrations may be an altered reinnervation pattern of neurones responsible for processing visual information. This appears to be the 1st case described with a persisting continuously visual perception disorder induced most likely by chronic MDMA use. (PsycINFO Database Record © 2008 APA, all rights reserved)

Patterson, C. D. (1974). Self-reported unpleasant effects from illicit use of fourteen substances The British Journal of Addiction to Alcohol and Other Drugs, 69(3), 249-256.

Pedersen, W., & Skrondal, A. (1999). Ecstasy and new patterns of drug use: A normal population study Addiction (Abingdon, England), 94(11), 1695-1706.

AIMS: (i) To describe illegal drug use patterns in an adolescent normal population sample with special emphasis on MDMA, ecstasy; (ii) to investigate where ecstasy is introduced in a hypothesized drug use sequence, and (iii) to contrast the predictors of ecstasy use with those of other illegal substances. Special attention was given to the relationship to subcultural music preferences and house-party-going. DESIGN: A school-based survey of the total cohort of adolescents enrolled in the school system in a city. PARTICIPANTS: 10,812 adolescents, age 14-17 years, response rate 94.3%. SETTING: Oslo, the capital and only metropolitan town in Norway. MEASUREMENTS: Social class was measured by the occupation standard ISCO 88, questions were posed as regards frequency of alcohol use and alcohol intoxication, cigarette smoking and use of cannabis, amphetamines, ecstasy and heroin. Alcohol problems were measured by a shortened version of Rutgers Alcohol Problem Index (RAPI), conduct problems were measured according to the four categories of acts forming the basis of the diagnosis conduct disorder in DSM-IV, internalizing mental health problems were measured using items from Hopkins Symptoms Checklist (HCL). A number of questions were asked as regards subcultural music preferences and house-party-going. STATISTICAL MODELS: A hypothesized cumulative sequence in drug use was investigated by means of latent class analysis, and the predictors of the various patterns of drug use were estimated and compared by means of multinominal logistic regression analysis. FINDINGS: The use of ecstasy was often intermingled with the use of cannabis, amphetamines and heroin, in a pattern of polydrug use. The latent class analysis revealed the following drug use sequence: (1) alcohol, (2) cigarettes, (3) cannabis, (4) amphetamines, (5) ecstasy and (6) heroin. There was no significant association between ecstasy use and parental social class or residential area of the town. All patterns of illegal drug use were highly associated with cigarette smoking, alcohol use, alcohol problems and conduct problems, whereas the associations with internalizing mental health problems were of less magnitude. Multinominal logistic regression analysis revealed that the use of ecstasy (E) was significantly more weakly associated with cigarette smoking than were the use of cannabis only ©, amphetamines (A) and the combination of ecstasy and amphetamines (A + E). The association between E and conduct problems (CP) was weaker than the association between CP and A and A + E. Finally, there were associations between E and A + E and House/Techno preferences and house-party-going, which were not found for C and A. CONCLUSIONS: Ecstasy is used by adolescents who use other legal and illegal substances in a polydrug-use pattern. The substance is introduced late in a hypothesized drug use sequence. Even so, ecstasy use seems to differ from the use of, e.g. amphetamines, in that the association with smoking and conduct problems is weaker and that the associations with subcultural music preferences and house-party-going are much stronger.

Pelissolo, A., Maniere, F., Boutges, B., Allouche, M., Richard-Berthe, C., & Corruble, E. (2007). Anxiety and depressive disorders in 4,425 long term benzodiazepine users in general practice [Troubles anxieux et depressifs chez 4 425 patients consommateurs de benzodiazepines au long cours en medecine generale ] L’Encephale, 33(1), 32-38.

Consumption rates of anxiolytic drugs, and especially of benzodiazepines, remain very high in France compared to other Western countries, whereas clinical guidelines limit their indications to short term treatments and only for some precise anxiety disorders. Recent epidemiologic surveys in the community indicated that more than 15% of people used once or more an anxiolytic drug in the past year. The issue of chronic treatments is particularly crucial because of their poor benefit/risk ratio in most anxiety disorders (limited efficacy, cognitive side effects, withdrawal and dependence problems). To address this important public health issue, and knowing that, in France, benzodiazepines are prescribed mainly by general physicians, our aims were to explore psychiatric diagnoses in GP’s patients with chronic use of anxiolytic benzodiazepines. We included 4 425 patients consuming such drugs regularly for six months or more, and assessed their anxiety and depression symptoms through various clinical scales (Hospital Anxiety and Depressive scale – HAD, Clinical Global Impression scale – CGI, Sheehan Disability Scale – SDS, Cognitive Dependence to Benzodiazepines scale – CDB) and with the Mini International Neuropsychiatric Interview for DSM IV criteria. Only 2.2% of the subjects had neither anxious nor depressive symptoms as indicated by low scores on both subscores (less than icon_cool.gif of the HAD scale, used as a screener. Nearly three quarters of the 4,257 subjects (73.2%), had CGI scores of at least 5 (markedly ill to extremely ill). Social and familial disability was also high in more than 40% of the sample (marked to extreme disruption according to SDS scores). About half of the sample had CDB scores suggesting a benzodiazepine dependence. According to the MINI, 85.1% of the patients had at least one current DSM IV diagnosis of affective disorder. The most frequent diagnoses were major depressive episode (60%), generalized anxiety disorder (61.2%), and panic disorder (22.5%). An anxiety and depressive comorbidity wad found in 41.9% of the subjects. Some methodological limitations must be taken into account in the discussion of our results, and especially the fact that the included patients were not supposed to be totally representative of all patients consuming anxiolytic benzodiazepines in general practice. However, the size of our sample is sufficiently large to limit possible biases in patient selection. The main result of this study is that a great majority of the patients had significant symptomatology, in particular major depressive episodes and generalized anxiety disorder, often with marked severity and disability. These data are in line with the knowledge of a lack of efficacy of benzodiazepines in depressive and most anxiety disorders, despite long term treatment. They also confirm the current guidelines which recommend prescribing serotoninergic antidepressants, and not benzodiazepines, when long term treatments are needed for severe and chronic affective disorders. This epidemiologic study leads to the conclusion that a specific and attentive diagnostic assessment should be done in all patients receiving benzodiazepines for more than three months, in order to purpose in many cases other long term therapeutic strategies.

Picker, W., Lerman, A., & Hajal, F. (1992). Potential interaction of LSD and fluoxetine The American Journal of Psychiatry, 149(6), 843-844.

Pierce, P. A., & Peroutka, S. J. (1988). Antagonism of 5-hydroxytryptamine2 receptor-mediated phosphatidylinositol turnover by d-lysergic acid diethylamide The Journal of Pharmacology and Experimental Therapeutics, 247(3), 918-925.

The interactions of the indolealkylamine hallucinogen d-lysergic acid diethylamide (d-LSD) and two phenalkylamine hallucinogens, 2,5-dimethoxy-4-bromoamphetamine (DOB) and 2,5-dimethoxy-4-iodoamphetamine (DOI), with 5-hydroxytryptamine2 (5-HT2) receptors were analyzed in rat cortex using both radioligand binding techniques and biochemical measurements of phosphatidylinositol (PI) turnover. 5-HT2 binding sites were labeled by [3H]ketanserin. DOB and DOI displayed decreased affinity for 5-HT2 sites in the presence of 10(-4) M GTP, whereas the ability of d-LSD to compete for these sites was not affected by the presence of 10(-4) M GTP. Moreover, the Hill slope of the d-LSD competition curve was unity in both the absence and presence of 10(-4) M GTP. These findings suggest that d-LSD is an antagonist at 5-HT2 receptors. PI turnover studies in rat cortex showed that at 10(-5) M concentrations d-LSD, DOB and DOI display partial agonist activity in comparison to 10(-5) 5-HT. Stimulation of PI turnover by 5-HT, DOB and DOI was inhibited by the 5-HT2 antagonist ketanserin (10(-6) M). The d-LSD PI signal was not affected by the presence of ketanserin. In addition, nanomolar concentrations of d-LSD did not stimulate PI turnover in rat cortex. Moreover, nanomolar concentrations of d-LSD are able to significantly antagonize the stimulatory effect of 10(-5) M 5-HT on PI turnover. These data suggest that d-LSD acts as an antagonist at 5-HT2 receptors in rat cortex. At high concentrations (greater than 1 microM) d-LSD stimulates low-level PI turnover via a non-5-HT2 receptor-mediated mechanism.

Pjrek, E., Winkler, D., Stastny, J., Praschak-Rieder, N., Willeit, M., & Kasper, S. (2007). Escitalopram in seasonal affective disorder: Results of an open trial Pharmacopsychiatry, 40(1), 20-24. doi:10.1055/s-2007-958718

OBJECTIVE: The aim of this study was to evaluate the efficacy and tolerability of escitalopram in the treatment of seasonal affective disorder (SAD, fall-winter depression). METHODS: Twenty SAD patients were included in an 8-week drug surveillance. Patients were treated with open-label escitalopram at a dosage of 10 to 20 mg per day. Efficacy assessments included the Structured Interview Guide for the Hamilton Depression Rating Scale (SAD version; SIGH-SAD), the Clinical Global Impression (CGI) and the Social Adaptation Self Evaluation Scale (SASS). Side effects were monitored with the UKU Side Effect Rating Scale. RESULTS: From week 2 onwards, escitalopram significantly reduced SIGH-SAD score and CGI severity score (p

Primavera, L. H., & Pascal, R. (1986). A comparison of male users and nonusers of marijuana on the perceived harmfulness of drugs The American Journal of Drug and Alcohol Abuse, 12(1-2), 71-77.

Subjects (n = 108) who volunteered to participate in a study in which they expected to smoke marijuana were asked, as part of a screening procedure, to rate the harmfulness of a number of illicit drugs including marijuana. Subjects were separated into three groups according to their reported history of use of marijuana. The three groups were: naive users (at least 1 but no more than 25 incidences of use in a lifetime), light users (1 to 3 incidences of use per week), and heavy users (at least 5 incidences of use per week). Groups did not differ in terms of their perceived harmfulness of any of the drugs. Cluster analyses of the results for each group and for the total group indicated three distinct clusters: the drugs perceived to be the most harmful were heroin, morphine, and LSD; drugs perceived to be less harmful were cocaine, amphetamines, barbiturates, and nicotine; and the drugs perceived to be the least harmful were caffeine and marijuana, with marijuana being judged the least harmful of all the drugs.

Raifman, M. A., & Berant, M. (1978). Flying high with angel dust American Journal of Diseases of Children (1960), 132(4), 432-433.

Rickert, V. I., Siqueira, L. M., Dale, T., & Wiemann, C. M. (2003). Prevalence and risk factors for LSD use among young women Journal of Pediatric and Adolescent Gynecology, 16(2), 67-75.

STUDY OBJECTIVE: To report the lifetime prevalence of lysergic acid diethylamide (LSD) and to identify unique correlates of using this substance in the last year among a large multiethnic sample of sexually active adolescent and young adult women aged 14 to 26 yrs. DESIGN, SETTING, PARTICIPANTS: A cross-sectional survey, administered at university-based ambulatory reproductive health clinics, was completed by 904 women between April and November of 1997 to identify risk factors associated with their use of LSD within the past 12 months. Subjects who reported lifetime, but not past 12 months’, use of marijuana, LSD, or other illicit drugs were excluded, leaving a sample of 368 nonusers and 56 users of LSD. In addition, 231 young women who reported only using marijuana in the last year were used as a comparison group to identify unique factors associated with LSD use. RESULTS: Of the total sample (n=904), 13% (n=119) reported lifetime use of LSD, and 58% (n=536) reported lifetime use of marijuana. Logistic regression analyses controlling for age and race/ethnicity found distinct profiles for those who reported using LSD or only marijuana in the last year when compared to those who reported no substance use. Common to both groups was reporting being drunk at least 10 times during the last year, regular smoking of at least half a pack of cigarettes, and identification as a high-sexual-risk taker. However, LSD users as compared to nonusers were more likely to report white ethnicity (as compared to nonwhite), be less than or equal to 17 years of age (as compared to at least 18 years), report a history of physical abuse, and be categorized as having severe depressive symptomatology. In contrast, those who reported only using marijuana were more likely to report single marital status, young age at first intercourse, having half or more of their friends use marijuana, and poor grades. CONCLUSIONS: The female LSD user presents a distinct profile that might aid clinicians in identifying potential LSD use in this population as well as alerting clinicians to the relationship between LSD use and high-risk sexual behaviors.

Rinkel, M. (1965). LSD: Problems connected with its use, misuse, and abuse in the united states Recent Advances in Biological Psychiatry, 8, 103-113.

Rosen, D. H., & Hoffman, A. M. (1972). Focal suicide: Self-enucleation by two young psychotic individuals The American Journal of Psychiatry, 128(8), 1009-1012.

Rossi, G. V. (1971). LSD–a pharmacologic profile. American Journal of Pharmacy and the Sciences Supporting Public Health, 143(2), 38-44.

Saidel, D. R., & Babineau, R. (1976). Prolonged LSD flashbacks as conversion reactions. Journal of Nervous & Mental Disease, 163(5), 352-355.

This paper presents a case study of the background and treatment of a patient with prolonged LSD flashbacks. The hypothesis that flashbacks can be psychologically determined symptoms is supported by the dynamics of the case and the course of treatment. A second focus is a partial explanation for the often made observation that obessive-compulsive personalities are at increased risk for LSD flashbacks (Copyright applies to all Abstracts.)

Sanders-Bush, E., Burris, K. D., & Knoth, K. (1988). Lysergic acid diethylamide and 2,5-dimethoxy-4-methylamphetamine are partial agonists at serotonin receptors linked to phosphoinositide hydrolysis The Journal of Pharmacology and Experimental Therapeutics, 246(3), 924-928.

Based on electrophysiological, radioligand binding, and behavioral studies in laboratory animals, it is generally believed that the psychotomimetic effects of the phenethylamine and indolealkylamine hallucinogens are mediated by central serotonin (5-HT) receptors, in particular the 5-HT-2 subtype. Agonist-stimulated phosphoinositide hydrolysis was utilized to determine the potency and efficacy of racemic 1-(2,5)-dimethoxy-4-methyl-phenyl)-2-aminopropane (DOM), and d-lysergic acid diethylamide (LSD) at the 5-HT-2 receptor in rat cerebral cortex and the 5-HT-1c receptor in rat choroid plexus. Both DOM and LSD stimulated phosphoinositide hydrolysis in cerebral cortex. These effects were blocked by the 5-HT-2 antagonists, ketanserin and spiperone, but not by antagonists of muscarinic, alpha-1 adrenergic or histaminergic receptors. The maximum responses of DOM and LSD, respectively, were 76% and 25% of the maximum response to 5-HT. However, LSD was 500 times more potent than was racemic DOM. Consistent with a partial agonist effect, LSD partially blocked the effect of 5-HT, with a maximal inhibition equivalent to the intrinsic activity of LSD alone. In choroid plexus, DOM and LSD stimulated phosphoinositide hydrolysis and both responses were blocked by mianserin and less effectively by spiperone. The maximum effect of DOM was 67% of that of 5-HT, whereas the maximum effect of LSD was only 34% of the maximum response of 5-HT. LSD was 50 times more potent than was racemic DOM. LSD partially antagonized the effect of 5-HT in the choroid plexus, consistent with a partial agonist effect at the 5-HT-1c receptor in this tissue.(ABSTRACT TRUNCATED AT 250 WORDS)

Satinder, K. P., & Black, A. (1984). Cannabis use and sensation-seeking orientation The Journal of Psychology, 116(1st Half), 101-105.

Cannabis use and its relationship with sensation-seeking orientation was investigated in 48 college and university students of both sexes. Users and nonusers were matched for sex, age, and education. Cannabis users scored higher on all the four subscales of the sensation-seeking scale (SSS). Analysis of covariance controlling for the use of alcohol, cigarettes, and LSD decreased the level of significance between the user and nonuser groups on all the subscales and the total SSS scores; however, the differences between the user and nonuser remained significant on the disinhibition subscale and the total SSS scores.

Scott, M. E. (1971). The flashback phenomenon Virginia Medical Monthly, 98(6), 317-320.

Sertraline and persistent LSD flashback in depress student.(1997). Brown University Psychopharmacology Update, 8(9), 10.

Presents a case report on the effectiveness of sertraline on the treatment of LSD-like phenomenon in a depressed student. Exacerbation of symptoms initially.

Siegenthaler, G. (1971). Problems with narcotics [Rauschgiftprobleme ] Schweizerische Monatsschrift Fur Zahnheilkunde = Revue Mensuelle Suisse d’Odonto-Stomatologie / SSO, 81(11), 1132-1138.

Silling, S. M. (1980). LSD flashbacks: An overview of the literature for counselors. American Mental Health Counselors Association Journal, 2(1), 38-45.

Surveyed the literature to delineate the etiology of LSD flashbacks. Concluded that adverse experiences while using LSD are predictive of flashbacks; physiological effects of LSD use may linger after the drug has been metabolized; and individuals who have flashbacks are highly suggestive and play a flashback “role.”

Simon, N. M., Worthington, J. J., Doyle, A. C., Hoge, E. A., Kinrys, G., Fischmann, D., et al. (2004). An open-label study of levetiracetam for the treatment of social anxiety disorder The Journal of Clinical Psychiatry, 65(9), 1219-1222.

OBJECTIVE: Social anxiety disorder is a disabling condition characterized by excessive fear and avoidance of social and performance situations. While a variety of effective pharmacotherapies exists, many patients do not fully respond to or tolerate available agents. Preclinical and early clinical experience with levetiracetam, a novel anticonvulsant agent, suggests that levetiracetam has anxiolytic properties and a favorable adverse event profile. Levetiracetam thus warrants systematic evaluation as a treatment option for anxiety disorders. METHOD: Twenty adult outpatients who were recruited through advertisement and clinical referral and who met DSM-IV criteria for social anxiety disorder, generalized type, participated in this 8-week open-label, flexible-dose study from November 2002 to December 2003. Participants were required to have scores of >/= 50 on the Liebowitz Social Anxiety Scale (LSAS) and >/= 4 on the Clinical Global Impressions-Severity of Illness scale (CGI-S) at baseline. The presence of comorbid depression and anxiety disorders were permitted as long as social anxiety disorder was the primary disorder. Levetiracetam was initiated at 250 mg/day for the first week and flexibly titrated up to a maximum of 3000 mg/day (1500 mg b.i.d.). The primary outcome measure was change in the LSAS score at endpoint. RESULTS: There was a clinically significant 20.5-point decrease in LSAS scores in the intent-to-treat, last-observation-carried-forward analysis (t = 3.1; p

Sinnett, E. R. (1976). Temporal patterns of drug use – a pilot study Perceptual and Motor Skills, 43(3 pt. 1), 793-794.

Examination of pilot data for classes of drugs showed significant coefficients of concordance for ranked times of most common to least common use. Marijuana, psychedelics, and amphetamines were used most commonly from 6 to 10 p.m., coincidental with temporal patterns for viewing television suggests recreational use. Use times for caffeine were completely different.

Smart, R. G., & Bateman, K. (1967). Unfavourable reactions to LSD: A review and analysis of the available case reports Canadian Medical Association Journal, 97(20), 1214-1221.

Smith, J. A., Walters, G., & Johnston, D. (1980). LSD ‘flashback’ as a cause of diagnostic error Postgraduate Medical Journal, 56(656), 421-422.

An emaciated, but otherwise physically normal young man presented with an acute psychosis resembling hallucinogenic drug abuse. His behaviour was so strange that the underlying pathology of severe pyloric stenosis was only detected when a chance measurement of urea and electrolytes was made, revealing gross biochemical abnormalities. His abnormal mental state persisted for more than one week and an LSD ‘flashback’ was postulated as the cause of the prolonged psychosis

Snyder, S. H., Faillace, L., & Hollister, L. (1967). 2,5-dimethoxy-4-methyl-amphetamine (STP): A new hallucinogenic drug Science (New York, N.Y.), 158(801), 669-670.

We have assessed the effects in normal control volunteers of 2,5-dimethoxy-4-methyl-amphetamine, the chemical present in the hallucinogenic drug STP, in two independent trials. In low doses, this compound produces a mild euphoria. Doses greater than 3 milligrams may cause pronounced hallucinogenic effects lasting about 8 hours and similar to those produced by hallucinogenic doses of lysergic acid diethylamide, mescaline, and psilocybin. 2,5-Dimethoxy-4-methyl-amphetamine, which is chemically related to mescaline and amphetamine, is about 100 times more potent as a hallucinogen than mescaline and only one-thirtieth as potent as lysergic acid diethylamide. Its psychological effects are not accentuated by chlorpromazine.

Solhkhah, R., Finkel, J., & Hird, S. (2000). Possible risperidone-induced visual hallucinations. Journal of the American Academy of Child & Adolescent Psychiatry, 39(9), 1074-1075.

Risperidone is sometimes used in children and adolescents to treat psychotic disorders and bipolar disorder, and in adults with a history of hallucinogen use who have hallucinogen-persisting perception disorder (HPPD). However, some recent reports have described cases in which adults treated with risperidone demonstrated induced or exacerbated HPPD symptoms. The case is reported of an 18-yr-old female who was born to a heroin-addicted mother and had a diagnosis of bipolar I disorder and polysubstance dependence, including hallucinogen use. Upon hospital admission for manic and psychotic symptoms, risperidone was started. On Day 5, the S experienced new-onset visual hallucinations. Because the patient reported no visual hallucinations at admission, the authors believed the most likely cause was HPPD, possibly induced by risperidone. The risperidone was discontinued, and the S was started on olanzapine. On this regimen her manic and psychotic symptoms remitted. The case demonstrates the need for caution when prescribing neuroleptic medications in children and adolescents. (PsycINFO Database Record © 2008 APA, all rights reserved)

Stanton, M. D., & Bardoni, A. (1972). Drug flashbacks: Reported frequency in a military population The American Journal of Psychiatry, 129(6), 751-755.

Stanton, M. D., Mintz, J., & Franklin, R. M. (1976). Drug flashbacks. II. some additional findings The International Journal of the Addictions, 11(1), 53-69.

A subsample was drawn from an earlier collection of data in order to answer a number of questions related to “acid” (LSD, STP) flashbacks. Acid users who reported flashbacks also reported significantly more marijuana use than those who did not; the two groups did not differ on use of other drugs, including acid. Simple correlations and multiple regression analyses both showed extent of marijuana use to be the only drug variable significantly related to acid flashbacks. No optimal combination of marijuana and acid improved flashback prediction. Among acid users, correlations between amounts of use for various drugs were high and significant, excepting only the marijuana-acid correlation.

Strassman, R. J. (1984). Adverse reactions to psychedelic drugs. A review of the literature The Journal of Nervous and Mental Disease, 172(10), 577-595.

The use of naturally occurring and synthetically derived compounds for their “psychedelic” effects has been a part of human culture for thousands of years. The basic pharmacology of the major synthetic psychedelic compounds (primarily lysergic acid diethylamide [LSD]-25) is described and reference is made to their potentially beneficial psychological effects. Adverse reactions, defined as dysphoric and/or maladaptive/dysfunctional responses to the use of these drugs, sometimes require careful clinical judgment in order to diagnose. These reactions can be effectively classified along a temporal continuum. Acute, short-lived reactions are often fairly benign, whereas chronic, unremitting courses carry a poor prognosis. Delayed, intermittent phenomena (“flashbacks”) and LSD-precipitated functional disorders that usually respond to treatment appropriate for the non-psychedelic-precipitated illnesses they resemble, round out this temporal means of classification. The question of organic brain damage as well as permanent changes in personality, attitudes, and creativity in patients and normals who have repeatedly ingested psychedelic drugs is controversial, but tends to point to subtle or nonsignificant changes. Future areas for study of the psychedelics’ pharmacological, psychological, and therapeutic effects are suggested.

Sunness, J. S. (2004). Persistent afterimages (palinopsia) and photophobia in a patient with a history of LSD use Retina (Philadelphia, Pa.), 24(5), 805.

Tec, L. (1972). Staccato syndrome as a consequence of drug abuse International Pharmacopsychiatry, 7(1-4), 101-104.

Thurlow, H. J., & Girvin, J. P. (1971). Use of anti-epileptic medication in treating “flashbacks” from hallucinogenic drugs Canadian Medical Association Journal, 105(9), 947-948.

Tietz, W. (1967). Complications following ingestion of LSD in a lower class population California Medicine, 107(5), 396-398.

A study was made of 49 patients observed at Los Angeles County Hospital as a direct result of LSD ingestion. In 57 per cent of these patients an extended psychosis developed although they had no previous history of psychotic behavior. The patients were young and of low socio-economic order. Those who were discharged from the County Hospital made poor social adjustment in succeeding months.

Trulson, M. E., Heym, J., & Jacobs, B. L. (1981). Dissociations between the effects of hallucinogenic drugs on behavior and raphe unit activity in freely moving cats Brain Research, 215(1-2), 275-293.

The hypothesis that the action of hallucinogenic drugs is mediated by a depression of the activity of brain serotonergic (raphe) neurons was tested by examining the behavioral effects of several hallucinogenic drugs while concurrently monitoring the activity of raphe neurons in freely moving cats. LSD produced a dose-dependent decrease in raphe unit activity and a dose-dependent increase in certain behaviors (e.g. limb flick and abortive groom), and the peak of the behavioral and unit changes were temporally correlated. However, there were three important dissociations between the behavioral and electrophysiological effects of LSD. Firstly, low doses of LSD produced only small decreases in raphe unit activity but significant behavioral changes. Secondly, the duration of LSD-induced behavioral changes significantly outlasted the depression of raphe unit activity. And thirdly, raphe neurons were at least as responsive to LSD during tolerance as they were in the nontolerant condition. Psilocin produced a dose-dependent decrease in raphe unit activity, while the behavioral changes were not dose-related. However, the peak behavioral changes corresponded to the maximal depression of raphe unit activity. The phenylethylamine hallucinogens, DOM and mescaline, both produced large behavioral changes but no overall effect on raphe neurons. Following administration of DOM or mescaline, some raphe units showed a significant increase, while some showed a significant decrease, and others showed no change in activity. Therefore, the phenylethylamine hallucinogens may exert a depressant effect upon a subset of serotonin-containing neurons, and an amphetamine-like excitatory effect upon another subset of these neurons. Consistent with previous studies, all hallucinogens produced a high concentration of slow waves in the cortical EEG. Following administration of LSD or psilocin, the appearance of slow waves in the EEG was often associated with a transitory decrease in unit activity, while this was not observed for the phenylethylamine hallucinogens. The present data, in conjunction with recent data from other laboratories, suggest that the serotonin hypothesis of hallucinogenic drug action should be re-evaluated.

Ungerleider, J. T., Fisher, D. D., & Fuller, M. (1966). The dangers of LSD. analysis of seven months’ experience in a university hospital’s psychiatric service JAMA : The Journal of the American Medical Association, 197(6), 389-392.

Valenca, A. M., Nardi, A. E., Mezzasalma, M. A., Nascimento, I., Lopes, F. L., Zin, W. A., et al. (2004). Clonidine in respiratory panic disorder subtype Arquivos De Neuro-Psiquiatria, 62(2B), 396-398. doi:/S0004-282X2004000300004

OBJECTIVE: Clonidine, which inhibits locus coeruleus discharge, would seem for theoretical reasons to be a good antipanic drug. Panic disorder (PD) presents a heterogeneous cluster of symptoms and a classification based on subtypes has been suggested and the respiratory symptoms group appears as a distinct subtype. METHOD: We report three cases of respiratory PD patients who were successfully treated with clonidine. RESULTS: Patients obtained panic free status, reduced anxiety levels and better functioning after clonidine administration (0.30-0.45 mg/day) for 6 weeks. CONCLUSION: Clonidine can be effective in the treatment of respiratory PD. This drug might play a role in relieving symptoms of anxiety due to noradrenergic hyperactivity in these patients.

Vieta, E., Goikolea, J. M., Corbella, B., Benabarre, A., Reinares, M., Martinez, G., et al. (2001). Risperidone safety and efficacy in the treatment of bipolar and schizoaffective disorders: Results from a 6-month, multicenter, open study The Journal of Clinical Psychiatry, 62(10), 818-825.

BACKGROUND: The goal of this study was to assess the efficacy and safety of risperidone in bipolar and schizoaffective disorders. METHOD: 541 patients entered this open, multicenter, 6-month study. Patients were entered provided that they fulfilled DSM-IV criteria for bipolar disorder or schizoaffective disorder, bipolar type, during a manic, hypomanic, mixed, or depressive episode. Risperidone was added to any previous mood-stabilizing medication that the patients were taking. Efficacy was assessed with the Young Mania Rating Scale (YMRS), the Hamilton Rating Scale for Depression (HAM-D), the Positive and Negative Syndrome Scale (PANSS), and the Clinical Global Impressions scale (CGI). Extrapyramidal symptoms (EPS) were assessed using the UKU Side Effect Rating Scale. RESULTS: 430 patients completed the study. Addition of risperidone produced highly significant improvements (p

Vieta, E., Herraiz, M., Fernandez, A., Gasto, C., Benabarre, A., Colom, F., et al. (2001). Efficacy and safety of risperidone in the treatment of schizoaffective disorder: Initial results from a large, multicenter surveillance study. group for the study of risperidone in affective disorders (GSRAD) The Journal of Clinical Psychiatry, 62(8), 623-630.

BACKGROUND: An adequate therapy for psychotic disorders needs to be effective against mood as well as psychotic symptoms. Analyses of data from clinical trials of risperidone in schizophrenia and small open-label studies in mania suggest that risperidone may have this broad efficacy profile. We present data on a 6-week trial of risperidone for the treatment of schizoaffective disorder that was part of a larger, 6-month surveillance study of patients with affective disorders. METHOD: One hundred two patients suffering from schizoaffective disorder (DSM-IV or ICD-10) entered the trial. Inclusion criteria consisted of a current DSM-IV diagnosis of schizoaffective disorder, bipolar type; DSM-IV manic or mixed psychotic episode; and a Young Mania Rating Scale (YMRS) score > 7 for a mixed episode (> 20 for a manic episode). Assessments included the YMRS, the Positive and Negative Syndrome Scale (PANSS), the Hamilton Rating Scale for Depression (HAM-D), the 4-item Clinical Global Impressions (CGI) scale, and the UKU Side Effect Rating Scale subscale for neurologic side effects. For patients entering the study, open-label risperidone therapy was added to their existing regimens of mood-stabilizing treatments. Other antipsychotic drugs were not allowed. RESULTS: Ninety-five patients completed the 6-week trial. At week 6, the mean +/- SD dose of risperidone was 4.7+/-2.5 mg/day. The mean scores on the assessment scales at baseline and week 6 (unless otherwise stated) were as follows: YMRS, 22.7 and 4.7, an improvement of 18.0 points (p

VOJTECHOVSKY, M. (1964). Cholinotropic hallucinogens. ii. [CHOLINOTROPN'I HALUCINOGENY. II ] Lekarska Veda v Zahranici, 35, 69-73.

Waltzer, H. (1972). Depersonalization and the use of LSD: A psychodynamic study American Journal of Psychoanalysis, 32(1), 45-52.

Weller, R. A., & Halikas, J. A. (1980). Objective criteria for the diagnosis of marijuana abuse The Journal of Nervous and Mental Disease, 168(2), 98-103.

Among 97 chronic marijuana users, 9% were found to have had multiple life problems as a consequence of their marijuana use when evaluated during a 5-year follow-up study. Operationally defined criteria for marijuana abuse are presented which are analogous to criteria commonly used in diagnosing alcoholism. These criteria identified marijuana abusers who manifested many problems from marijuana use, including fighting, panic attacks, and traffic tickets. This was in contrast to the majority of the chronic users who did not have multiple complications from their marijuana use. The marijuana abusers had used marijuana more frequently, had used greater amounts of marijuana, and had begun using it at an earlier age than nonabusers. A high rate of alcoholism was found in the abusers but was not statistically greater than in nonabusers. The objective criteria presented here offer a method for simple, prompt evaluation of potential problems from marijuana use.

Wesson, D. R., & Smith, D. E. (1976). An analysis of psychedelic drug flashbacks The American Journal of Drug and Alcohol Abuse, 3(3), 425-438.

Psychedelic drug flashbacks have been a puzzling clinical phenomenon observed by clinicians. Flashbacks are defined as transient, spontaneous recurrences of the psychedelic drug effect appearing after a period of normalcy following an intoxication of psychedelics. The paper traces the evolution of the concept of flashback and gives examples of the varieties encountered. Although many drugs have been advocated for the treatment of flashback, flashbacks generally decrease in intensity and frequency with abstinence from psychedelic drugs.

Wiesbeck, G. A., & Taeschner, K. L. (1991). A cerebral computed tomography study of patients with drug-induced psychoses European Archives of Psychiatry and Clinical Neuroscience, 241(2), 88-90.

Twelve male patients with chronic drug consumption including cannabis (ICD = 304.3) and morphine (ICD = 304.7), who required inpatient treatment for drug-induced paranoid hallucinatory states (ICD = 292.1) were investigated using computed tomography for macroscopic structural changes in the brain. The findings were compared with those in a control group of schizophrenic patients who did not consume drugs. The brain scans were measured and not show any significant morphological differences between the two groups.

Woody, G. E. (1970). Visual disturbances experienced by hallucinogenic drug abusers while driving The American Journal of Psychiatry, 127(5), 683-686.

WOODY, G. E. (1971). Hallucinogens and afterimages. American Journal of Psychiatry, 128(3), 367-a.

Wu, L. T., Pilowsky, D. J., & Schlenger, W. E. (2005). High prevalence of substance use disorders among adolescents who use marijuana and inhalants Drug and Alcohol Dependence, 78(1), 23-32. doi:10.1016/j.drugalcdep.2004.08.025

BACKGROUND: We examined the association between the use of inhalants, marijuana, and other drugs and recent DSM-IV substance use disorders among adolescents aged 12-17 years. METHODS: Data were drawn from 2000 to 2001 National Household Surveys on Drug Abuse. Adolescents aged 12-17 years who reported having ever used an illicit drug in their lifetime were categorized into four mutually exclusive groups: inhalant users (16%), marijuana users (53%), inhalant and marijuana users (16%), and other drug users (15%). Logistic regression models were used to estimate associations with recent substance use diagnoses among lifetime adolescent drug users (N=10,180). RESULTS: We found that 31% of lifetime drug users reported having never used marijuana. One half of these atypical drug users were predominantly nonmedical users of pain relievers. Adolescents who used inhalants or other drugs but not marijuana were least likely to report multidrug use. Adolescents who reported using both inhalants and marijuana were most likely to use three or more classes of drugs (73%) and to receive a diagnosis of past year alcohol (35%) and drug (39%) abuse or dependence. CONCLUSIONS: Our study findings suggest that among lifetime adolescent drug users, those who use both inhalants and marijuana are at very high risk for alcohol and drug use disorders.

Wu, L. T., Schlenger, W. E., & Galvin, D. M. (2006). Concurrent use of methamphetamine, MDMA, LSD, ketamine, GHB, and flunitrazepam among american youths Drug and Alcohol Dependence, 84(1), 102-113. doi:10.1016/j.drugalcdep.2006.01.002

BACKGROUND: The magnitude and the characteristics of the use of methamphetamine, MDMA (Ecstasy), LSD (d-lysergic acid diethylamide), ketamine, GHB (gamma-hydroxybutyrate), and flunitrazepam (Rohypnol) were examined in a probability sample of the U.S. civilian population that included multiethnic urban, suburban, and rural youths aged 16-23 (N=19,084). METHODS: Data were drawn from the National Survey on Drug Use and Health (NSDUH). Logistic regression analyses were conducted to identify the characteristics associated with the use of each of these drugs and of multiple drugs. RESULTS: Approximately 20% of youths aged 16-23 reported having ever used one or more of these drugs. Less than 1% of club drug users used club drugs only, and 82% of them had ever used three or more drug classes. Females were more likely than males to report using multiple club drugs. Recent users of methamphetamine were most likely to be females and adolescents aged 16 or 17. Recent users of MDMA tended to be young adults aged 18-21 and residents of metropolitan areas. Most recent users of LSD were adolescents aged 16-19 and those in low-income families. Ketamine users were primarily employed youths. Staying in school and getting married were associated with decreased odds of club drug use. Club drug use was highly associated with the presence of criminal behaviors and recent alcohol abuse or dependence. CONCLUSIONS: Adolescents are more likely than young adults to use multiple drugs. The clustering of multidrug use and alcohol use disorder is a cause of concern.

Yager, J., Crumpton, E., & Rubenstein, R. (1983). Flashbacks among soldiers discharged as unfit who abused more than one drug The American Journal of Psychiatry, 140(7), 857-861.

Of 280 soldiers discharged from military service in 1971 as unfit, 207 reported the heavy use of at least one drug (most of these abused more than one drug) and 146 (52%) reported having flashbacks. Most flashbacks were of a simple visual nature, but repeat “trips,” complex subjective experiences, and persistent difficulties in concentration were often reported. The prevalence and severity of flashbacks increased with drug use, particularly with hallucinogens and marijuana. Because psychological, social, and physiological factors may all contribute to flashback phenomena, other populations need to be studied to determine the extent to which these findings can be generalized.

Young, C. R. (1997). Sertraline treatment of hallucinogen persisting perception disorder. Journal of Clinical Psychiatry, 58(2), 85-85.

Reports the case of a 22-yr-old man who presented with hallucinogen persisting perception disorder and symptoms of mild depression 6 mo after discontinuing the use of LSD. Antidepressant treatment was begun with sertraline, until a target dose of 100 mg was reached. Mild exacerbations of the LSD-like phenomena were noted for 2-4 days after each dosage increase. Within 1 mo of reaching the target dose the perceptual disturbances decreased until they had almost completely remitted, and the depressive symptoms also improved. It is hypothesized that hallucinogen persisting perception disorder is serotonergically mediated, and that sertraline initially exacerbates the perceptual disturbances, but attenuates them after chronic administration. (PsycINFO Database Record © 2008 APA, all rights reserved)

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