Hallucinogen persisting perception disorder (HPPD) is rarely encountered in clinical settings. It is described as a re-experiencing of some perceptual distortions induced while intoxicated and suggested to subsequently cause functional impairment or anxiety. Two forms exist: Type 1, which are brief “flashbacks,” and Type 2 claimed to be chronic, waxing, and waning over months to years. A review of HPPD is presented. In addition, data from a comprehensive survey of 20 subjects reporting Type-2 HPPD-like symptoms are presented and evaluated. Dissociative Symptoms are consistently associated with HPPD. Results of the survey suggest that HPPD is in most cases due to a subtle over-activation of predominantly neural visual pathways that worsens anxiety after ingestion of arousal-altering drugs, including non-hallucinogenic substances. Individual or family histories of anxiety and pre-drug use complaints of tinnitus, eye floaters, and concentration problems may predict vulnerability for HPPD. Future research should take a broader outlook as many perceptual symptoms reported were not first experienced while intoxicated and are partially associated with pre-existing psychiatric comorbidity.
Multiple
Do Hallucinogens Cause Residual Neuropsychological Toxicity?
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.
Hallucinogens on the Internet: A Vast New Source of Underground Drug Information
OBJECTIVE: The illicit use of hallucinogens is reemerging in the United States, especially among well-educated adults and teenagers. These same groups are also frequent users of the Internet. The authors sought to characterize the extent of information about hallucinogens available to Internet users. METHOD: Using standard Internet search techniques, the authors located 81 hallucinogen-related sites and categorized the information provided. RESULTS: Internet sites offer thousands of pages of information—albeit of questionable accuracy—on how to obtain, synthesize, extract, identify, and ingest hallucinogens. Much of this information has yet to appear in textbooks. By contrast, the authors found few U.S. government agency sites offering cautionary material about hallucinogen use. CONCLUSIONS: Using the Internet, potential hallucinogen users can bypass traditional channels of medical information and learn in great detail how to obtain and use numerous drugs with unknown hazards.
Hallucinogen Persisting Perception Disorder: What Do We Know After 50 Years?
‘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.
Hallucinogen Use Disorders
KEY POINTS
Perceptions among adolescents regarding hallucinogens use are changing. Current trends show there are increasing emergency department presentations from use of these drugs.
Use of novel hallucinogens, such as 25I-NBOMe, is gaining popularity and can have serious medical complications.
Hallucinogen use may result in psychiatric disorders that may occur at time of use or afterward and may cause secondary psychotic, mood, or anxiety disorders. Limited data exist regarding treatment of these psychiatric disorders in adolescents, and evidence is extrapolated from adult studies. Benzodiazepines and behavioral techniques are recommended first-line treatments. Certain antipsychotics may worsen hallucinogen disorders and should be used with caution.
Evaluating the Abuse Potential of Psychedelic Drugs As Part of the Safety Pharmacology Assessment for Medical Use in Humans
Psychedelics comprise drugs come from various pharmacological classes including 5-HT2A agonists, indirect 5-HT agonists, e.g., MDMA, NMDA antagonists and κ-opioid receptor agonists. There is resurgence in developing psychedelics to treat psychiatric disorders with high unmet clinical need. Many, but not all, psychedelics are schedule 1 controlled drugs (CDs), i.e., no approved medical use. For existing psychedelics in development, regulatory approval will require a move from schedule 1 to a CD schedule for drugs with medical use, i.e., schedules 2–5. Although abuse of the psychedelics is well documented, a systematic preclinical and clinical evaluation of the risks they pose in a medical-use setting does not exist. We describe the non-clinical tests required for a regulatory evaluation of abuse/dependence risks, i.e., drug-discrimination, intravenous self-administration and physical dependence liability. A synopsis of the existing data for the various types of psychedelics is provided and we describe our findings with psychedelic drugs in these models. FDA recently issued its guidance on abuse/dependence evaluation of drug-candidates (CDER/FDA, 2017). We critically review the guidance, discuss the impact this document will have on non-clinical abuse/dependence testing, and offer advice on how non-clinical abuse/dependence experiments can be designed to meet not only the expectations of FDA, but also other regulatory agencies. Finally, we offer views on how these non-clinical tests can be refined to provide more meaningful information to aid the assessment of the risks posed by CNS drug-candidates for abuse and physical dependence.
This article is part of the Special Issue entitled ‘Psychedelics: New Doors, Altered Perceptions’.
What Do We Know About the Risks of Psychedelics?
For starters, assessing risk is tricky. A lot of what both scientists and the general public think they know about the potential risks of psychedelic use comes from the first wave of research and experimentation in the 1950s, 60s and 70s. But this body of knowledge includes studies that wouldn’t meet today’s scientific standards; urban legends; and sensational, unsubstantiated news stories.
Also, reporting and describing adverse events is often subjective to some extent, psychiatrist Rick Strassman noted in a 1984 paper. Some people consider the drug-induced state itself pathological, he wrote, while others believe even the worst reactions are part of “throwing off ‘straight’ society’s ‘shackles’ and in reaching a ‘higher’ level of consciousness.” And many of the more recent studies on the potential harms of LSD and other hallucinogens draw on data from the 1950s and 60s. Those studies had a lot of methodological problems; many lack baseline data about their subjects, didn’t use placebos and/or failed to specify the source of the drug or the setting in which it was given.
Therapeutic Guidelines: Dangers and Contraindications in Therapeutic Applications of Hallucinogens
INTRODUCTION There are widespread beliefs about the dangers of hallucinogenic drugs and frequent media reports attributing fatalities to hallucinogens. This media bias was typical in the early 1970s when much attention was focused on supposed chromosome damage and birth defects in children born to mothers who had taken LSD (lysergic acid diethylamide) during pregnancy. Later on, negative results of better-controlled, rigorous investigations (Muneer 1978) refuted the earlier alarmist concerns, but these received very little attention in the media. The controversial nature of the U.S. drug policy and its influence on government-sponsored research of illicit drugs has recently drawn media attention due to investigational flaws of highly publicized research claiming harmful effects (Jennings 2003).
The Adverse Effects of Hallucinogens From Intramural Perspective
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.
Entheogens and Existential Intelligence: The Use of Plant Teachers As Cognitive Tools Source
In light of recent specific liberalizations in drug laws in some countries, I have investigated the potential of entheogens (i.e., psychoactive plants used as spiritual sacraments) as tools to facilitate existential intelligence. “Plant teachers” from the Americas such as ayahuasca, psilocybin mushrooms, and peyote, and the Indo-Aryan soma of Eurasia, are examples of entheogens that have been used used in both the past and present. These have all been revered as spiritual or cognitive tools to provide a richer cosmological understanding of the world for both individuals and cultures. I used Gardner’s (1999a) revised multiple intelligence theory and his postulation of an “existential” intelligence as a theoretical lens through which to account for the cognitive possibilities of entheogens and explore potential ramifications for education.