A Review of Hallucinogen Persisting Perception Disorder (HPPD) and an Exploratory Study of Subjects Claiming Symptoms of HPPD.

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.

The association of psychedelic use and opioid use disorders among illicit users in the United States.

BACKGROUND: Preliminary studies show psychedelic compounds administered with psychotherapy are potentially effective and durable substance misuse interventions. However, little is known about the association between psychedelic use and substance misuse in the general population. This study investigated the association between psychedelic use and past year opioid use disorders within illicit opioid users. METHODS: While controlling for socio-demographic covariates and the use of other substances, the relationship between classic psychedelic use and past year opioid use disorders was analyzed within 44,000 illicit opioid users who completed the National Survey on Drug Use and Health from 2008 to 2013. RESULTS: Among respondents with a history of illicit opioid use, psychedelic drug use is associated with 27% reduced risk of past year opioid dependence (weighted risk ratio = 0.73 (0.60-0.89) p = 0.002) and 40% reduced risk of past year opioid abuse (weighted risk ratio = 0.60 (0.41-0.86) p = 0.006). Other than marijuana use, which was associated with 55% reduced risk of past year opioid abuse (weighted risk ratio = 0.45 (0.30-0.66) p < 0.001), no other illicit drug was associated with reduced risk of past year opioid dependence or abuse. CONCLUSION: Experience with psychedelic drugs is associated with decreased risk of opioid abuse and dependence. Conversely, other illicit drug use history is largely associated with increased risk of opioid abuse and dependence. These findings suggest that psychedelics are associated with positive psychological characteristics and are consistent with prior reports suggesting efficacy in treatment of substance use disorders.

Effects of 3,4-Methylenedioxymethamphetamine on Patient Utterances in a Psychotherapeutic Setting.

3,4-Methylenedioxymethamphetamine (MDMA) administered as an adjunct to talk therapy influences patient speech content and increases improvement in treatment-resistant posttraumatic stress disorder (PTSD). Data came from the recordings of Mithoefer et al. (2011). In the third therapeutic session studied, patients were assigned, double blind, to an MDMA or a placebo group. Condition-blind scorers listened to therapy recordings and scored utterances where patients initiated topics that were empathic (regarding others' emotions), entactic (requesting or appreciating physical touch), or ensuic (describing a change in their sense of themselves). Patients who received MDMA produced high levels of ensuic, empathic, and entactic utterances compared with those who received the placebo. Interrater discourse scoring was reliable. The relationship between the number of scored utterances and the Clinician Administered PTSD Scale scores measuring PTSD severity after the treatment was significant, and reanalysis grouped bimodally into "many" or "few" such utterances remained significant. MDMA assisted these patients in having meaningful and disorder-resolving thoughts and discourse in talk therapy.

Mitigation of post-traumatic stress symptoms by Cannabis resin: a review of the clinical and neurobiological evidence.

It is known from clinical studies that some patients attempt to cope with the symptoms of post-traumatic stress disorder (PTSD) by using recreational drugs. This review presents a case report of a 19-year-old male patient with a spectrum of severe PTSD symptoms, such as intense flashbacks, panic attacks, and self-mutilation, who discovered that some of his major symptoms were dramatically reduced by smoking cannabis resin. The major part of this review is concerned with the clinical and preclinical neurobiological evidence in order to offer a potential explanation of these effects on symptom reduction in PTSD. This review shows that recent studies provided supporting evidence that PTSD patients may be able to cope with their symptoms by using cannabis products. Cannabis may dampen the strength or emotional impact of traumatic memories through synergistic mechanisms that might make it easier for people with PTSD to rest or sleep and to feel less anxious and less involved with flashback memories. The presence of endocannabinoid signalling systems within stress-sensitive nuclei of the hypothalamus, as well as upstream limbic structures (amygdala), point to the significance of this system for the regulation of neuroendocrine and behavioural responses to stress. Evidence is increasingly accumulating that cannabinoids might play a role in fear extinction and antidepressive effects. It is concluded that further studies are warranted in order to evaluate the therapeutic potential of cannabinoids in PTSD.

Genuine and drug-induced synesthesia: a comparison.

Despite some principal similarities, there is no systematic comparison between the different types of synesthesia (genuine, acquired and drug-induced). This comprehensive review compares the three principal types of synesthesia and focuses on their phenomenological features and their relation to different etiological models. Implications of this comparison for the validity of the different etiological models are discussed. Comparison of the three forms of synesthesia show many more differences than similarities. This is in contrast to their representation in the literature, where they are discussed in many respects as being virtually similar. Noteworthy is the much broader spectrum and intensity with the typical drug-induced synesthesias compared to genuine and acquired synesthesias. A major implication of the phenomenological comparison in regard to the etiological models is that genuine and acquired synesthesias point to morphological substrates, while drug-induced synesthesia appears to be based on functional changes of brain activity.

Residual neurocognitive features of long-term ecstasy users with minimal exposure to other drugs.

AIMS: In field studies assessing cognitive function in illicit ecstasy users, there are several frequent confounding factors that might plausibly bias the findings toward an overestimate of ecstasy-induced neurocognitive toxicity. We designed an investigation seeking to minimize these possible sources of bias. DESIGN: We compared illicit ecstasy users and non-users while (1) excluding individuals with significant life-time exposure to other illicit drugs or alcohol; (2) requiring that all participants be members of the 'rave' subculture; and (3) testing all participants with breath, urine and hair samples at the time of evaluation to exclude possible surreptitious substance use. We compared groups with adjustment for age, gender, race/ethnicity, family-of-origin variables and childhood history of conduct disorder and attention deficit hyperactivity disorder. We provide significance levels without correction for multiple comparisons. SETTING: Field study. PARTICIPANTS: Fifty-two illicit ecstasy users and 59 non-users, aged 18-45 years. MEASUREMENTS: Battery of 15 neuropsychological tests tapping a range of cognitive functions. FINDINGS: We found little evidence of decreased cognitive performance in ecstasy users, save for poorer strategic self-regulation, possibly reflecting increased impulsivity. However, this finding might have reflected a pre-morbid attribute of ecstasy users, rather than a residual neurotoxic effect of the drug. CONCLUSIONS: In a study designed to minimize limitations found in many prior investigations, we failed to demonstrate marked residual cognitive effects in ecstasy users. This finding contrasts with many previous findings-including our own-and emphasizes the need for continued caution in interpreting field studies of cognitive function in illicit ecstasy users.

The pharmacology of lysergic acid diethylamide: a review.

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.

"Enhanced" interrogation of detainees: do psychologists and psychiatrists participate?

After revelations of participation by psychiatrists and psychologists in interrogation of prisoners at Guantánamo Bay and Central Intelligence Agency secret detention centers, the American Psychiatric Association and the American Psychological Association adopted Position Statements absolutely prohibiting their members from participating in torture under any and all circumstances, and, to a limited degree, forbidding involvement in interrogations. Some interrogations utilize very aggressive techniques determined to be torture by many nations and organizations throughout the world. This paper explains why psychiatrists and psychologists involved in coercive interrogations violate the Geneva Conventions and the laws of the United States. Whether done with ignorance of professional ethical obligations or not, these psychiatrists and psychologists have crossed an ethical barrier that may best be averted from re-occurring by teaching medical students and residents in all medical specialties about the ethics principles stemming from the 1946-1947 Nuremberg trials and the Geneva Conventions, together with the Ethics Codes of the World Medical Association and the American Medical Association; and, with regard to psychiatric residents and psychological trainees, by the teaching about The Principles of Medical Ethics With Annotations Especially Applicable to Psychiatry and the Ethical Principles of Psychologists and Code of Conduct, respectively. In this way, all physicians and psychologists will clearly understand that they have an absolute moral obligation to "First, do no harm" to the human beings they professionally encounter.

Evidence of health and safety in American members of a religion who use a hallucinogenic sacrament.

BACKGROUND: Ayahuasca is a South American hallucinogenic tea used as a sacrament by the Santo Daime Church, other religions, and traditional peoples. A recent U.S. Supreme Court decision indicates religious ayahuasca use is protected, but little is known about health consequences for Americans. MATERIAL/METHODS: 32 (out of 40) American members of one branch of the Santo Daime Church were interviewed providing demographic information, physical exam, drug use timeline, a variety of psychological measures, and data about childhood conduct disorder. Subjects were asked about extent of Church participation, what is liked least and most about ayahuasca, and what health benefits or harms they attribute to ayahuasca. RESULTS: Members usually attend services weekly (lifetime 269+/-314.7 ceremonies; range 20-1300). Physical exam and test scores revealed healthy subjects. Members claimed psychological and physical benefits from ayahuasca. 19 subjects met lifetime criteria for a psychiatric disorder, with 6 in partial remission, 13 in full remission, and 8 reporting induction of remission through Church participation. 24 subjects had drug or alcohol abuse or dependence histories with 22 in full remission, and all 5 with prior alcohol dependence describing Church participation as the turning point in their recovery. CONCLUSIONS: Conclusions should not be extrapolated to hallucinogen abusers of the general public. For those who have religious need for ingesting ayahuasca, from a psychiatric and medical perspective, these pilot results substantiate some claims of benefit, especially if subjects interviewed fully reflect general membership. Further research is warranted with blinded raters, matched comparison groups, and other measures to overcome present study limitations.

Self-treatment of opioid withdrawal using kratom (Mitragynia speciosa korth).

BACKGROUND: Kratom (Mitragynia speciosa korth) is recognized increasingly as a remedy for opioid withdrawal by individuals who self-treat chronic pain. CASE DESCRIPTION: A patient who had abruptly ceased injection hydromorphone abuse self-managed opioid withdrawal and chronic pain using kratom. After co-administering the herb with modafinil he experienced a tonic-clonic seizure, but he reported only modest abstinence once kratom administration stopped. We confirmed the identity of the plant matter he ingested as kratom and identified no contaminants or adulterants. We also conducted high-throughput molecular screening and the binding affinity at mu, delta and kappa receptors of mitragynine. CONCLUSION: We report the self-treatment of chronic pain and opioid withdrawal with kratom. The predominant alkaloid of kratom, mitragynine, binds mu- and kappa-opioid receptors, but has additional receptor affinities that might augment its effectiveness at mitigating opioid withdrawal. The natural history of kratom use, including its clinical pharmacology and toxicology, are poorly understood.

Response of cluster headache to psilocybin and LSD.

The authors interviewed 53 cluster headache patients who had used psilocybin or lysergic acid diethylamide (LSD) to treat their condition. Twenty-two of 26 psilocybin users reported that psilocybin aborted attacks; 25 of 48 psilocybin users and 7 of 8 LSD users reported cluster period termination; 18 of 19 psilocybin users and 4 of 5 LSD users reported remission period extension. Research on the effects of psilocybin and LSD on cluster headache may be warranted.

Psychological and cognitive effects of long-term peyote use among Native Americans.

BACKGROUND: Hallucinogens are widely used, both by drug abusers and by peoples of traditional cultures who ingest these substances for religious or healing purposes. However, the long-term residual psychological and cognitive effects of hallucinogens remain poorly understood. METHODS: We recruited three groups of Navajo Native Americans, age 18-45: 1) 61 Native American Church members who regularly ingested peyote, a hallucinogen-containing cactus; 2) 36 individuals with past alcohol dependence, but currently sober at least 2 months; and 3) 79 individuals reporting minimal use of peyote, alcohol, or other substances. We administered a screening interview, the Rand Mental Health Inventory (RMHI), and ten standard neuropsychological tests of memory and attentional/executive functions. RESULTS: Compared to Navajos with minimal substance use, the peyote group showed no significant deficits on the RMHI or any neuropsychological measures, whereas the former alcoholic group showed significant deficits (p < .05) on every scale of the RMHI and on two neuropsychological measures. Within the peyote group, total lifetime peyote use was not significantly associated with neuropsychological performance. CONCLUSIONS: We found no evidence of psychological or cognitive deficits among Native Americans using peyote regularly in a religious setting. It should be recognized, however, that these findings may not generalize to illicit hallucinogen users.

Hallucinogenic botanicals of America: a growing need for focused drug education and research.

Botanical sources for medicines in America have been known since long before the arrival of Columbus. Nevertheless, both scientists and the general public are often unaware that some of these botanical drugs are also potent intoxicants. We provide a quick overview of hallucinogenic and dissociative drugs harvested from nature or that are openly and legally cultivated in the United States. Examples of harmful outcomes reported in the media are contrasted with existing responsible ingestion by others, some of whom have the protected right to do so for traditional or sacramental religious purposes. Despite an ongoing and expensive effort to warn people of the potential harms of recreational drug use, little is known about the extent of use of these psychoactive botanicals, and the recent explosion of information available via the Internet could herald a storm of morbidity to come. Mounting more targeted research and educational efforts today may reduce later use and abuse, inform society about the special circumstances of religious use, and better prepare clinicians and other health care providers about the issues involved when people choose to indigenously source psychoactive drugs for human consumption.

Now is the time for AAPL to demonstrate leadership by advocating positions of social importance.

The American Academy of Psychiatry and the Law (AAPL) and other medical organizations have not taken a position on the abolition of capital punishment because of a long-standing tradition of remaining neutral on "nonmedical" societal issues that are highly divisive. It is the authors' contention that taking a stand on vital social issues that are clearly in the public interest is wholly consistent with the stated purposes of AAPL and that the time has come for an open and frank discussion by the membership on the merits of altering its policy, with particular focus on eliminating the death penalty. The present article explains why capital punishment can no longer be considered a nonmedical societal issue and why AAPL must awaken to take on controversial matters such as this one. For AAPL to continue to avoid this debate and silence any attempt to organize opposition to the current status quo will only serve to embolden those who argue in favor of the death penalty. Such continued silence betrays any notion of neutrality and is an abdication of the canons of medical ethics we have all sworn to uphold.

Residual neuropsychological effects of illicit 3,4-methylenedioxymethamphetamine (MDMA) in individuals with minimal exposure to other drugs.

BACKGROUND: A substantial literature suggests that users of illicit 3,4-methylenedioxymethamphetamine (MDMA or "ecstasy") display residual cognitive deficits. Most MDMA users, however, use other illicit drugs as well, so it is difficult to be certain that these deficits are due to MDMA, as opposed to other drug use or additional confounding factors. METHODS: We administered a battery of neuropsychological tests to 23 young MDMA users who reported minimal exposure to any other drugs, including alcohol, and to 16 comparison individuals equally involved with the rave subculture, but reporting no MDMA use. We compared the groups by regression analyses adjusting for numerous potentially confounding variables. To test for a possible dose-response effect, we also performed a median split of 12 moderate MDMA users (22-50 lifetime uses) and 11 heavy users (60-450 uses), and compared these subgroups with non-users. RESULTS: MDMA users as a whole performed worse than non-users on most test measures, but these comparisons rarely reached statistical significance. This picture changed markedly in the subgroup analysis: although moderate users displayed virtually no differences from non-users on any measures, the heavy users displayed significant deficits on many measures, particularly those associated with mental processing speed and impulsivity. These differences did not appear explainable by differences in family-of-origin variables, verbal IQ, levels of depression, or time since last MDMA use. CONCLUSIONS: The presence of residual cognitive deficits, even among unusually "pure" frequent users of illicit MDMA, analyzed with adjustment for confounding variables, augments the evidence that MDMA itself, rather than some associated factor, is responsible for the deficits observed.

Hallucinogens and dissociative agents naturally growing in the United States.

It is usually believed that drugs of abuse are smuggled into the United States or are clandestinely produced for illicit distribution. Less well known is that many hallucinogens and dissociative agents can be obtained from plants and fungi growing wild or in gardens. Some of these botanical sources can be located throughout the United States; others have a more narrow distribution. This article reviews plants containing N,N-dimethyltryptamine, reversible type A monoamine oxidase inhibitors (MAOI), lysergic acid amide, the anticholinergic drugs atropine and scopolamine, or the diterpene salvinorin-A (Salvia divinorum). Also reviewed are mescaline-containing cacti, psilocybin/psilocin-containing mushrooms, and the Amanita muscaria and Amanita pantherina mushrooms that contain muscimol and ibotenic acid. Dangerous misidentification is most common with the mushrooms, but even a novice forager can quickly learn how to properly identify and prepare for ingestion many of these plants. Moreover, through the ever-expanding dissemination of information via the Internet, this knowledge is being obtained and acted upon by more and more individuals. This general overview includes information on the geographical range, drug content, preparation, intoxication, and the special health risks associated with some of these plants. Information is also offered on the unique issue of when bona fide religions use such plants as sacraments in the United States. In addition to the Native American Church's (NAC) longstanding right to peyote, two religions of Brazilian origin, the Santo Daime and the Uniao do Vegetal (UDV), are seeking legal protection in the United States for their use of sacramental dimethyltryptamine-containing "ayahuasca."

Use of schizophrenia as a metaphor in US newspapers.

Research has identified misleading and stigmatizing popular beliefs about schizophrenia, but little is known about media images corresponding to these beliefs. Building on Susan Sontag's exploration of cancer in the 1978 book Illness as Metaphor, the authors hypothesize that "schizophrenia" is now more commonly misused. A total of 1740 newspaper articles from 1996 or 1997 that mentioned schizophrenia or cancer were randomly selected and then coded for contextual and metaphorical use. Only 1 percent of articles that mentioned cancer used that illness in a metaphorical way, compared with 28 percent of the articles that mentioned schizophrenia. Results differed by newspaper but not by region. The authors suggest that these inaccurate metaphors in the media contribute to the ongoing stigma and misunderstandings of psychotic illnesses.