OPEN Foundation

HPPD

Psilocybin – Summary of knowledge and new perspectives

Abstract

Psilocybin, a psychoactive alkaloid contained in hallucinogenic mushrooms, is nowadays given a lot of attention in the scientific community as a research tool for modeling psychosis as well as due to its potential therapeutic effects. However, it is also a very popular and frequently abused natural hallucinogen. This review summarizes all the past and recent knowledge on psilocybin. It briefly deals with its history, discusses the pharmacokinetics and pharmacodynamics, and compares its action in humans and animals. It attempts to describe the mechanism of psychedelic effects and objectify its action using modern imaging and psychometric methods. Finally, it describes its therapeutic and abuse potential.

Tylš, F., Páleníček, T., & Horáček, J. (2014). Psilocybin – Summary of knowledge and new perspectives. European Neuropsychopharmacology, 24, 342-365. http://dx.doi.org/10.1016/j.euroneuro.2013.12.006

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Hallucinogen persisting perception disorder: what do we know after 50 years?

Abstract

‘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.

Halpern, J. H., & Harrison, G. P. Jr. (2003). Hallucinogen persisting perception disorder: what do we know after 50 years? Drug and Alcohol Dependence, 69(2), 109-119. http://dx.doi.org/10.1016/S0376-8716(02)00306-X
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Abnormal visual experiences in individuals with histories of hallucinogen use: A web-based questionnaire

Abstract

Despite longstanding reports of prolonged or reoccurring perceptual changes in a subset of hallucinogen users, very little is known about Hallucinogen Persisting Perception Disorder and related visual abnormalities in hallucinogen users. We used an online questionnaire to document the symptoms and relationship to drug use of unusual visual phenomena in hallucinogen users. 16,192 individuals viewed the information sheet and 2679 were included in the study. Of these, 224 reported having unrelated diagnoses associated with unusual visual experiences and were excluded from main analyses. Most (60.6%) of the remaining 2455 participants reported having experienced drug-free visual experiences that resembled hallucinogen effects. Probability of experiencing constant or near-constant symptoms was predicted by greater past exposure to specific hallucinogens, including lysergic acid diethylamide (LSD). Although symptoms were common, few (104, or 4.2% of the sample) found them distressing or impairing enough to consider seeking treatment. Visual changes in hallucinogen users may be more common than previously suspected and are worthy of further study.

Baggott, M. J., Coyle, J. R., Erowid, E., Erowid, F., & Robertson, L. C. (2011). Abnormal visual experiences in individuals with histories of hallucinogen use: A web-based questionnaire. Drug and alcohol dependence, 114(1), 61-67. http://dx.doi.org/10.1016/j.drugalcdep.2010.09.006
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[Hallucinogen-induced psychological disorders]

Abstract

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.

Hermle, L., Kovar, K. A., Hewer, W., & Ruchsow, M. (2008). [Hallucinogen-induced psychological disorders]. Fortschritte der Neurologie-Psychiatrie, 76(6), 334-342. http://dx.doi.org/10.1055/s-2008-1038191
Link to full text [Article in German]

Hallucinogens: An update

Abstract

Research of hallucinogen abuse rarely extends beyond epidemiology and observed pathology. Even less research has been completed on the special circumstances surrounding the religious use of hallucinogens or on potential therapeutic applications. Rather than offer another basic review on the well-known hazards of illicit hallucinogen use, this paper provides an overview and practice recommendations on compounds the clinician may be less familiar with, such as the botanical plant Salvia divinorum, the drug 3,4-methylenedioxymethamphetamine (“ecstasy”) and synthetic hallucinogen analogs. The often-warned, but rarely occurring, hazard of hallucinogen persisting perception disorder (“flashbacks”) is also reviewed with treatment recommendations provided. The current status of clinical research with the hallucinogens is presented, with case vignettes suggesting hallucinogens may have anti-addictive applications. The special circumstances surrounding the religious, nondrug use of hallucinogens as sacred sacraments in the US and elsewhere are also presented. It is hoped that the reader will gain a more nuanced understanding of how these physiologically nonaddictive drugs may offer legitimate benefits in modern society. By appreciating that such benefits may one day be borne out by careful, methodologically sound research, clinicians should be better armed in raising the topic of hallucinogen use and abuse with their patients.

Halpern, J. H. (2003). Hallucinogens: an update. Current psychiatry reports, 5(5), 347-354. https://dx.doi.org/10.1007/s11920-003-0067-4

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Clonazepam treatment of lysergic acid diethylamide-induced hallucinogen persisting perception disorder with anxiety features.

Abstract

An unique and intriguing 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 one 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. The goal of our investigation was to assess the efficacy of clonazepam in the treatment of LSD-induced HPPD. Sixteen patients fulfilled entrance criteria. All complained of HPPD with anxiety features for at least 3 months and were drug free at least 3 months. They received clonazepam 2 mg/day for 2 months. Follow-up was continued for 6 months. They were weekly evaluated during the 2 months of clonazepam administration and monthly during the follow-up period using the Clinical Global Impression Scale, a Self-report Scale and Hamilton Anxiety Rating Scale. Patients 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-month follow-up period. This study suggests that high potency benzodiazepines like clonazepam, which has serotonergic properties, may be more effective than low-potency benzodiazepines in the treatment of some patients with LSD-induced HPPD.

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.
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Flashback and Hallucinogen Persisting Perception Disorder: clinical aspects and pharmacological treatment approach.

Abstract

One unique characteristic of lysergic acid diethylamide (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 clonazepan have been shown to ameliorate this syndrome in some of the individuals seeking treatment.

Lerner, A. G., Gelkopf, M., Skladman, I., & Oyffe, I. (2002). Flashback and hallucinogen persisting perception disorder: clinical aspects and pharmacological treatment approach. The Israel journal of psychiatry and related sciences, 39(2), 92.
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LSD-induced hallucinogen persisting perception disorder treatment with clonidine: an open pilot study.

Abstract

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 fulfilled entrance criteria. All complained of HPPD for at least 3 months and were drug free at least 3 months. They received fixed low doses of clonidine, 0.025 mg, three times a day for 2 months. They were evaluated by the Clinical Global Impression Scale (CGI) and a self-report scale on the severity of symptoms (graded 0-5). Patients scored an average of 5.25 (SD = 0.46) on the CGI and 4 on the self-report scale at baseline, indicating marked psychopathology. One patient dropped out at week 3 and a second patient dropped out at week 5. Of the six patients remaining at the end of 2 months, the average CGI score was 2.5 (SD = 0.55) 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.

Lerner, A. G., Gelkopf, M., Oyffe, I., Finkel, B., Katz, S., Sigal, M., & Weizman, A. (2000). LSD-induced hallucinogen persisting perception disorder treatment with clonidine: an open pilot study. International clinical psychopharmacology, 15(1), 35-37.
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30 April - Q&A with Rick Strassman

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