Search

There are few medications with demonstrated efficacy for the treatment of posttraumatic stress disorder (PTSD). Treatment guidelines have unequivocally designated psychotherapy as a first line treatment for PTSD. Yet, even after psychotherapy, PTSD often remains a chronic illness, with high rates of psychiatric and medical comorbidity. Meanwhile, the search for and development of drugs with new mechanisms of action has stalled. Therefore, there is an urgent need to explore not just novel compounds but novel approaches for the treatment of PTSD. A promising new approach involves the use of psychedelic drugs. Within the past few years, 2 psychedelics have received breakthrough designations for psychiatric indications from the US Food and Drug Administration, and several psychedelics are currently being investigated for the treatment of PTSD. This review discusses 4 types of compounds: 3,4-methylenedioxymethamphetamine, ketamine, classical psychedelics (e.g., psilocybin and lysergic acid diethylamide), and cannabinoids. We describe the therapeutic rationale, the setting in which they are being administered, and their current state of evidence in the treatment of PTSD. Each compound provides unique qualities for the treatment of PTSD, from their use to rapidly target symptoms to their use as adjuncts to facilitate psychotherapeutic treatments. Several questions are formulated that outline an agenda for future research.

Aims This heuristic study reports observations on the phenomenology of ayahuasca experiences of nine foreign tourist participants of an ayahuasca retreat in Peru. Methods Narrative interviews, reflecting individual experiences after ayahuasca “night ceremony,” have been analyzed by qualitative content analysis using a data-driven strategy in order to extract themes and categories inherent in the interviews. Previously, a demographic questionnaire was given. The dose–response connection was uncontrolled, which is typical for this naturalistic setting. Results The typical structure of spontaneously reported experiences includes: personal preparation, physical symptoms, visual phenomena, cognitive and emotional phenomena, reactions of the individual within the psychedelic “world” as well as within ordinary reality, and appraisal to the process. Emotional reactions were subsumed under pleasant (psychotherapeutic “target emotions” and hedonistic emotions) and unpleasant emotions. For a majority, the presence of psychotherapeutic target emotions seemed to involve the presence of unpleasant emotions in the same session – possibly as transitional emotional states. Conclusions This suggests that psychodynamic processes, for example, possible activation of emotional conflicts – can take place spontaneously, during ayahuasca intake in this particular setting. Some participants attributed symbolic meaning to the visionary content, which was more likely to take place in psychotherapeutically motivated clients. The specific setting influence as well as corresponding expectations of the participants in native wisdom could have considerable influence on experiences and interpretations, such as communication with entities as well as receiving personal teachings.

1-Propanoyl-lysergic acid diethylamide (1P-LSD) appeared as a non-controlled alternative to LSD a few years ago. Although evidence is beginning to emerge from in vitro and animal studies that 1P-LSD might serve as a prodrug for LSD, an equivalent evaluation in humans is unavailable. Controlled oral and intravenous self-administrations of 100 μg 1P-LSD hemitartrate are reported in two human volunteers followed by analyses of urine and serum samples using a fully validated LC-MS/MS method. Psychometric evaluations included assessment of selected subjective drug effects and administration of the Five-Dimensions of Altered States of Consciousness rating scale (5D-ASC). In serum and urine, oral administrations of 1P-LSD only led to the detection of LSD reflecting biphasic elimination with a terminal elimination half-life of approx. t1/2 = 6.4 h. 1P-LSD could be detected for only up to 4.16 h in serum and 2.7 h in urine following intravenous administration, whereas LSD was detected in all serum samples (last sampling after approx. 24 h) and up to 80 h in urine. LSD showed first order elimination kinetics with an approx. t1/2 = 5.7 h, whereas 1P-LSD showed a rapid decrease in concentration within the first hour followed by a slower decrease, most probably due to hydrolysis. The bioavailability of LSD after oral ingestion of 1P-LSD was close to 100%. The psychosensory effects of 1P-LSD and their time course were comparable to those seen after uptake of LSD in other studies which further supports the prodrug hypothesis. The 5D-ASC scores were higher after oral compared with intravenous administration of 1P-LSD.

Lysergic acid diethylamide (LSD) is a prototypical serotonergic psychedelic drug and the subject of many clinical investigations. In recent years, a range of lysergamides has emerged with the production of some being inspired by the existing scientific literature. Others, for example various 1-acyl substituted lysergamides, did not exist before their appearance as research chemicals. 1-Cylopropanoyl-LSD (1CP-LSD) has recently emerged as a new addition to the group of lysergamide-based designer drugs and is believed to be psychoactive in humans. In this investigation, 1CP-LSD was subjected to detailed analytical characterizations including various mass spectrometry (MS) platforms, gas and liquid chromatography, nuclear magnetic resonance spectroscopy, solid phase and GC condensed phase infrared spectroscopy. Analysis by GC-MS also revealed the detection of artificially induced degradation products. Incubation of 1CP-LSD with human serum led to the formation of LSD, indicating that it may act as a prodrug for LSD in vivo, similar to other 1-acyl substituted lysergamides. The analysis of blotters and pellets is also included. 1CP-LSD also induces the head-twitch response (HTR) in C57BL/6 J mice, indicating that it produces an LSD-like behavioural profile. 1CP-LSD induced the HTR with an ED50 = 430.0 nmol/kg which was comparable to 1P-LSD (ED50 = 349.6 nmol/kg) investigated previously. Clinical studies are required to determine the potency and profile of the effects produced by 1CP-LSD in humans.

ObjectivesThe international distribution and commodification of ayahuasca has created virtual communicative realms in the Internet in which members intensively exchange personal narratives, adverti...

This article describes the context in which 3,4-methylenedioxyamphetamine (MDA), 3,4-methylenedioxymethamphetamine (MDMA) and other mescaline-like compounds were explored as hallucinogens for military and intelligence purposes from the 1940s to the 1960s. Germans first tested mescaline as a "truth drug" in a military context. In the 1940s, the United States military started testing hallucinogenic substances as truth drugs for interrogation and behavior manipulation. After tests carried out using mescaline and other drugs in 1950, some derivatives of mescaline were synthesized by the Army for the exploration of possible "speech-inducing" effects. After insufficient animal testing, the substances were given to patients at the New York State Psychiatric Institute (NYSPI). 3,4-Methylenedioxy-N-ethylamphetamine (MDE), a compound almost identical to MDMA, was among the compounds delivered for testing at the NYSPI. During tests with other derivatives (3,4-dimethoxyphenethylamine (DMA), 3,4-methylenedioxyphenethylamine (MDPEA), MDA) in 1952-53, an unwitting patient died in these tests, which was kept secret from the public. Research was interrupted and toxicological animal testing procedures were initiated. The secret animal studies run in 1953/1954 revealed that some of the "mescaline derivatives" tested (e.g. MDA, MDE, DMA, 3,4,5-trimethoxyamphetamine (TMA), MDMA) were considered for further testing in humans. In 1955, the military changed focus to lysergic acid diethylamide (LSD), but some interest in mescaline-like compounds remained for their ability to change mood and habit without interfering with cognition and sensory perception. Based on the known documents, it remains unclear (but probable) whether any of the mescaline derivatives tested were being used operationally.

The psychedelic properties of lysergic acid diethylamide (LSD) have captured the imagination of researchers for many years and its rediscovery as an important research tool is evidenced by its clinical use within neuroscientific and therapeutic settings. At the same time, a number of novel LSD analogs have recently emerged as recreational drugs, which makes it necessary to study their analytical and pharmacological properties. One of the most recent additions to this series of LSD analogs is 1-butanoyl-LSD (1B-LSD), a constitutional isomer of 1-propionyl-6-ethyl-6-nor-lysergic acid diethylamide (1P-ETH-LAD), another LSD analog that was described previously. This study presents a comprehensive analytical characterization of 1B-LSD employing nuclear magnetic resonance spectroscopy (NMR), low- and high-resolution mass spectrometry platforms, gas- and liquid chromatography (GC and LC), and GC-condensed phase and attenuated total reflection infrared spectroscopy analyses. Analytical differentiation of 1B-LSD from 1P-ETH-LAD was straightforward. LSD and other serotonergic hallucinogens induce the head-twitch response (HTR) in rats and mice, which is mediated by 5-HT(2A) receptor activation. HTR studies were conducted in C57BL/6J mice to assess whether 1B-LSD has LSD-like behavioral effects. 1B-LSD produced a dose-dependent increase in HTR counts, acting with ~14% (ED(50) = 976.7 nmol/kg) of the potency of LSD (ED(50) = 132.8 nmol/kg). This finding suggests that the behavioral effects of 1B-LSD are reminiscent of LSD and other serotonergic hallucinogens. The possibility exists that 1B-LSD serves as a pro-drug for LSD. Further investigations are warranted to confirm whether 1B-LSD produces LSD-like psychoactive effects in humans.

The purpose of this chapter is to highlight the rich tradition of self-experiments (SEs) with psychoactive substances carried out by scientists and therapists for more than a century. Scientifically inspired controlled SEs dominated until the end of the twentieth century, when ethical requirements minimized controlled SEs and "wild" SEs expanded particularly with the emergence of new psychoactive substances. The review focuses on laughing gas (nitrous oxide), cannabis, cocaine, hallucinogens, entactogens, and dissociative hallucinogens. This is due to the fact that substances that induce "complex" effects such as alteration of space/time experience, ego dissolution, and increased feelings and insights (e.g., hallucinogens, entactogens) represent by far the majority of SEs, whereas SEs with substances inducing "simple" effects such as euphoria, anxiolysis, dissociation, or emotional blunting (e.g., cocaine, opioids) are much rarer or even absent (e.g., benzodiazepines). Complex drug effects are much harder to describe, thus allowing SEs to fulfill a more important function.SEs with psychoactive drugs appeared to emerge in the mid-eighteenth century, which triggered a long-standing tradition throughout the nineteenth and early twentieth century. SEs have been de facto performed for a variety of reasons, ranging from establishing scientific knowledge and gaining philosophical insights to compensating for personal deficits. Self-experimenters can be divided into two general types. Besides their scientific intentions, "exploratory" self-experimenters intend to expand awareness and insight, whereas "compensatory" self-experimenters might aim for coping with psychiatric symptoms or personality deficits. Scientific limitations of SEs are obvious when compared to double-blind, randomized, placebo-controlled trials. Whereas the former might lead to more "realistic" detailed description of subjective effects, the latter lead to more solid results in respect to objectively measurable "average" effects. Possible adverse effects of SEs were identified that resulted in loss of scientific objectivity and decreased control over substance use and addiction, development of isolation, problematic group dynamics, and "social autism."

There are conflicting interpretations of the evidence regarding the efficacy, tolerability, and safety of cannabinoids in pain management and palliative medicine.We conducted a systematic review (SR) of systematic reviews of randomized controlled trials (RCT) and prospective long-term observational studies of the use of cannabinoids in pain management and palliative medicine. Pertinent publications from January 2009 to January 2017 were retrieved by a selective search in the Cochrane Database of Systematic Reviews, the Database of Abstracts of Reviews of Effects, and Medline. The methodological quality of the SRs was assessed with the AMSTAR instrument, and the clinical relevance of quantitative data syntheses was assessed according to the standards of the Cochrane Collaboration.Of the 750 publications identified, 11 SRs met the inclusion criteria; 3 of them were of high and 8 of moderate methodological quality. 2 prospective long-term observational studies with medical cannabis and 1 with tetrahydrocannabinol/cannabidiol spray (THC/CBD spray) were also analyzed. There is limited evidence for a benefit of THC/CBD spray in the treatment of neuropathic pain. There is inadequate evidence for any benefit of cannabinoids (dronabinol, nabilone, medical cannabis, or THC/CBD spray) to treat cancer pain, pain of rheumatic or gastrointestinal origin, or anorexia in cancer or AIDS. Treatment with cannabis-based medicines is associated with central nervous and psychiatric side effects.The public perception of the efficacy, tolerability, and safety of cannabis-based medicines in pain management and palliative medicine conflicts with the findings of systematic reviews and prospective observational studies conducted according to the standards of evidence-based medicine.

The purpose of this chapter is to highlight the rich tradition of self-experiments (SEs) with psychoactive substances carried out by scientists and therapists for more than a century. Scientifically inspired controlled SEs dominated until the end of the twentieth century, when ethical requirements minimized controlled SEs and “wild” SEs expanded particularly with the emergence of new psychoactive substances. The review focuses on laughing gas (nitrous oxide), cannabis, cocaine, hallucinogens, entactogens, and dissociative hallucinogens. This is due to the fact that substances that induce “complex” effects such as alteration of space/time experience, ego dissolution, and increased feelings and insights (e.g., hallucinogens, entactogens) represent by far the majority of SEs, whereas SEs with substances inducing “simple” effects such as euphoria, anxiolysis, dissociation, or emotional blunting (e.g., cocaine, opioids) are much rarer or even absent (e.g., benzodiazepines). Complex drug effects are much harder to describe, thus allowing SEs to fulfill a more important function.

A double-blind, randomized, active placebo-controlled pilot study was conducted to examine safety and efficacy of lysergic acid diethylamide (LSD)-assisted psychotherapy in 12 patients with anxiety associated with life-threatening diseases. Treatment included drug-free psychotherapy sessions supplemented by two LSD-assisted psychotherapy sessions 2 to 3 weeks apart. The participants received either 200 μg of LSD (n = 8) or 20 μg of LSD with an open-label crossover to 200 μg of LSD after the initial blinded treatment was unmasked (n = 4). At the 2-month follow-up, positive trends were found via the State-Trait Anxiety Inventory (STAI) in reductions in trait anxiety (p = 0.033) with an effect size of 1.1, and state anxiety was significantly reduced (p = 0.021) with an effect size of 1.2, with no acute or chronic adverse effects persisting beyond 1 day after treatment or treatment-related serious adverse events. STAI reductions were sustained for 12 months. These results indicate that when administered safely in a methodologically rigorous medically supervised psychotherapeutic setting, LSD can reduce anxiety, suggesting that larger controlled studies are warranted.This is an open-access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivatives 3.0 License, where it is permissible to download and share the work provided it is properly cited. The work cannot be changed in any way or used commercially.

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.

MDMA (3,4-methylenedioxy-methylamphetamine, a.k.a. "ecstasy") was first synthesized in 1912 and resynthesized more than once for pharmaceutical reasons before it became a popular recreational drug. Partially based on previously overlooked U.S. government documentation, this article reconstructs the early history of MDMA as a recreational drug in the U.S. from 1960 to 1979. According to the literature, MDMA was introduced as a street drug at the end of the 1960s. The first forensic detection of MDMA "on the street" was reported in 1970 in Chicago. It appears that MDMA was first synthesized by underground chemists in search of "legal alternatives" for the closely related and highly sought-after drug MDA, which was scheduled under the Controlled Substances Act (CSA) in 1970. Until 1974, nearly all MDMA street samples seized came from the U.S. Midwest, the first "hot region" of MDMA use. In Canada, MDMA was first detected in 1974 and scheduled in 1976. From 1975 to 1979, MDMA was found in street samples in more than 10 U.S. states, the West Coast becoming the major "hot region" of MDMA use. Recreational use of MDMA spread across the U.S. in the early 1980s, and in 1985 it was scheduled under the CSA.

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.

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.

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.

Aims Alexander T. Shulgin is widely thought of as the ‘father’ of +/−3,4‐methylenedioxymethamphetamine (MDMA). This paper re‐assesses his role in the modern history of this drug. Methods We analysed systematically Shulgin's original publications on MDMA, his publications on the history of MDMA and his laboratory notebook. Results According to Shulgin's book PIHKAL (1991), he synthesized MDMA in 1965, but did not try it. In the 1960s Shulgin also synthesized MDMA‐related compounds such as 3,4‐methylenedioxyamphetamine (MDA), 3‐methoxy‐4,5‐methylenedioxyamphetamine (MMDA) and 3,4‐methylenedioxyethylamphetamine (MDE), but this had no impact on his rediscovery of MDMA. In the mid‐1970s Shulgin learned of a ‘special effect’ caused by MDMA, whereupon he re‐synthesized it and tried it himself in September 1976, as confirmed by his laboratory notebook. In 1977 he gave MDMA to Leo Zeff PhD, who used it as an adjunct to psychotherapy and introduced it to other psychotherapists. Conclusion Shulgin was not the first to synthesize MDMA, but he played an important role in its history. It seems plausible that he was so impressed by its effects that he introduced it to psychotherapist Zeff in 1977. This, and the fact that in 1978 he published with David Nichols the first paper on the pharmacological action of MDMA in humans, explains why Shulgin is sometimes (erroneously) called the ‘father’ of MDMA.

3,4-Methylenedioxymethamphetamine (MDMA), also known as ecstasy, was first synthesized in 1912 but first reached widespread popularity as a legal alternative after the much sought-after recreational drug 3,4-methylenedioxy-amphetamine (MDA) was made illegal in 1970. Because of its benign, feeling-enhancing, and nonhallucinatory properties, MDMA was used by a few dozen psychotherapists in the United States between 1977 and 1985, when it was still legal. This article looks into the contexts and practices of its psychotherapeutic use during these years. Some of the guidelines, recommendations, and precautions developed then are similar to those that apply to psychedelic drugs, but others are specific for MDMA. It is evident from this review that the therapists pioneering the use of MDMA were able to develop techniques (and indications/counterindications) for individual and group therapy that laid the groundwork for the use of MDMA in later scientific studies. In retrospect, it appears that the perceived beneficial effects of MDMA supported a revival of psycholytic/psychedelic therapy on an international scale.

Twenty-six in-patients with Diagnostic and Statistical Manual version IV (DSM-IV) criteria for opioid dependence were selected at random to receive either a combination of an 11-day low-dose buprenorphine and a 14-day carbamazepine regimen (n = 14) or a combination of an 11-day methadone and a 14-day carbamazepine regimen (n = 12) in a double-blind, randomized 14-day in-patient detoxification treatment. Patients with buprenorphine and carbamazepine showed a significantly better psychological state after the first and second weeks of treatment. Above all, the buprenorphine-treated patients demonstrated a less marked tiredness, sensitiveness and depressive state as well as a more prominent elevated mood during the detoxification process. Seven non-completers (after 7 days: four of 12 = 33.3%; after 14 days: seven of 12 = 58.3%) were treated with methadone and carbamazepine and five non-completers (after 7 days: two of 14 = 14.3%; after 14 days: five of 14 = 35.7%) received buprenorphine and carbamazepine. The difference in the overall dropout rate after day 14 was not significant. The present study supports the hypothesis that the combination of buprenorphine and carbamazepine leads to a better clinical outcome than does a combination of methadone and carbamazepine in the detoxification of opioid addicts with additional multiple drug abuse. The buprenorphine and carbamazepine-regimen provides a more effective short-term relief of affective disturbances than does methadone and carbamazepine. No severe side effects occurred during the treatment period in both groups.

Background Auditory hallucinations and passivity experiences are associated with an abnormality in the self-monitoring mechanism that normally allows us to distinguish self-produced from externally produced sensations. It is unclear if chronic central pain disorders such as fibromyalgia and somatoform pain disorders also involve a defect of the self-monitoring mechanism. Methods Responses to tactile stimulation were assessed in four groups of subjects (N = 40): patients with fibromyalgia, patients with somatoform pain disorder, patients with schizophrenia with auditory hallucinations and/or passivity experiences, and normal control subjects. The subjects were asked to rate the perception of a tactile sensation on their left and right hands. The tactile stimulation was either self-produced by movement of the subject's right or left hand or externally produced by the experimenter. Results Normal control subjects experienced self-produced stimuli as less intense than identical, externally produced tactile stimuli. In contrast, patients with fibromyalgia, patients with somatoform pain disorder, and patients with schizophrenia with auditory hallucinations and/or passivity experiences gave the same perceptual ratings for tactile stimuli produced by themselves as those produced by the experimenter (intergroup difference, p = .043; 95% confidence interval [CI], 0.16-0.68). Post hoc tests revealed that this significance was mainly caused by the fibromyalgia (p = .046; 95% CI, -1.66-0.13) and the somatoform pain disorder group (p = .033; 95% CI, -1.71-0.06). Conclusions We conclude that central pain disorders such as fibromyalgia and somatoform pain disorders interfere with the correct functioning of the self-monitoring mechanism that normally allows us to distinguish self-produced from externally produced tactile stimuli.

This is the first neuropsychological study using the S-enantiomer of the noncompetetive N-methyl-D-aspartate antagonist ketamine. In 2 randomized placebo-controlled trials we studied effects of two different doses of (S)-ketamine (low dose/high dose) on neuropsychological functions and psychopathology in 12 healthy male volunteers. Impairment was measured via standardized neuropsychological tests. Results indicate that both subanaesthetic doses produce only nonsignificant impairment in most of the tasks. Tasks involving divided and sustained attention as well as scores for objective and subjective psychopathology show significant impairment in a dose-dependent manner. Implications of these findings for the neuropsychology of attention and schizophrenia are discussed.

Methylenedioxymethamphetamine (MDMA or "Ecstasy") is a major stimulant drug of abuse worldwide. MDMA produces euphoria, enhances interpersonal communication and feelings of closeness with others. In contrast to the induced emotions of affection and sensual enhancement, clinical studies show that it impairs sexual drive and functioning. In drug-free humans, sexual stimulation with orgasm induces a pronounced secretion of prolactin, which may mediate the post-orgasmic state. The phenomenological features of the psychological state induced by MDMA show some similarities with features of the post-orgasmic state. In addition, MDMA also induces a prominent increase of prolactin plasma levels with a similar time kinetic compared to the post-orgasmic prolactin increase. Here, we present the hypothesis that the impairment of sexual parameters after MDMA may be mediated by increased prolactin.

Sexual arousal is accompanied by some typical physiological reaction patterns. Another typical feature of sexual intercourse is involuntary sound production implying in its more intense forms acceleration of breathing (hyperventilation). Up to now no study examined spCO2 during intense sexual intercourse, but there is evidence that some degree of hyperventilation with its physiological consequences may often be induced during sexual intercourse. This article discusses implications of hyperventilation during sexual intercourse for alterations of consciousness and subjective experience in the light of recent studies of brain metabolic changes during states of hyperventilation. Groaning and hyperventilation are interpreted in this context as a psychophysiological mechanism to deepen states of sexual trance.

Thirty-four alcoholics were treated with acupuncture to the ear and the body in a randomized single-blind placebo-controlled design over 14 days. Orthodox points and placebo needles to orthodox points were used daily for a total of 10 treatments starting on the first day of admission as add-on therapy to standard medication with carbamazepine. The primary outcome was the Clinical Institute Withdrawal Assessment (CIWA-Ar-scale) assessed on days 1-6, 9 and 14. No initial differences were found regarding sociodemographic data, drinking history and alcohol-related data, indicating successful randomization. Longitudinal analysis of the Clinical Institute Withdrawal Assessment (CIWA-Ar-scale) data showed that patients assigned to acupuncture had a general tendency towards better outcome results and significantly fewer withdrawal symptoms on day 14 (Wilcoxon-W=177.500, Z=-2.009, p = 0.045). No significant differences were found in the Beck Depression Inventory (BDI), State-Trait Anxiety Inventory (STAI X1 and X2) and Eigenschaftswoerterliste (EWL S60). We conclude that acupuncture as an adjunctive treatment to carbamazepine medication shows promise for the treatment of alcohol withdrawal symptoms. Further investigation of this treatment modality appears to be warranted.

Objective: A recently published study showed the safety and efficacy of LSD-assisted psychotherapy in patients with anxiety associated with life-threatening diseases. Participants of this study were included in a prospective follow-up. Method: 12 months after finishing LSD psychotherapy, 10 participants were tested for anxiety (STAI) and participated in a semi-structured interview. A Qualitative Content Analysis (QCA) was carried out on the interviews to elaborate about LSD effects and lasting psychological changes. Results: None of the participants reported lasting adverse reactions. The significant benefits as measured with the STAI were sustained over a 12-month period. In the QCA participants consistently reported insightful, cathartic and interpersonal experiences, accompanied by a reduction in anxiety (77.8%) and a rise in quality of life (66.7%). Evaluations of subjective experiences suggest facilitated access to emotions, confrontation of previously unknown anxieties, worries, resources and intense emotional peak experiences à la Maslow as major psychological working mechanisms. The experiences created led to a restructuring of the person’s emotional trust, situational understanding, habits and world view. Conclusions: LSD administered in a medically supervised psychotherapeutic setting can be safe and generate lasting benefits in patients with a life-threatening disease. Explanatory models for the therapeutic effects of LSD warrant further study.

Introduction: Synaesthesia is a phenomenon in which a certain stimulus induces a concurrent sensory perception; it has an estimated prevalence of 4%. Sexual arousal as an inducer for synaesthetic perceptions is rarely mentioned in the literature but can be found sometimes in case reports about subjective orgasmic experiences. Aims: To examine whether synaesthetic perceptions during sexual intercourse have an impact on the sexual experience and the extent of sexual trance compared to non-synaesthetes. Methods: In total, 19 synaesthetes with sexual forms of synaesthesia (17 female; 2 male) were included as well as corresponding control data of 36 non-synaesthetic subjects (n = 55). Two questionnaires were used to assess relevant aspects of sexual function and dysfunction (a German adaption of the Brief Index of Sexual Functioning, KFSP) as well as the occurrence and extent of sexual trance (German version of the Altered States of Consciousness Questionnaire, OAVAV). Additionally qualitative interviews were conducted in some subjects to further explore the nature of sexual experiences in synaesthetes. Main Outcome Measures: Sexual experience and extent of sexual trance during intercourse. Results: Synaesthetes depicted significantly better overall sexual function on the KFSP with increased scores for the subscale “sexual appetence” but coevally significant lower subscale scores for “sexual satisfaction.” Sexual dysfunction was not detected in this sample. Synaesthetes depicted significantly higher levels of the subscales “oceanic boundlessness” and “visionary restructuralization” than controls using the OAVAV. Qualitative interviews revealed varying synaesthetic perceptions during the different states of arousal. Furthermore, synaesthetes reported an unsatisfactory feeling of isolation caused by the idiosyncratic perceptions. Conclusions: Synaesthetes with sexual forms of synaesthesia seem to experience a deeper state of sexual trance without, however, enhanced satisfaction during sexual intercourse.

Cluster headache (CH) is a stereotyped primary headache characterized by strictly unilateral severe orbital or periorbital pain and categorized as either episodic or chronic (1,2). Its prevalence is 0.1% (3). Oxygen and sumatriptan are the treatments of choice for individual attacks, whereas verapamil, lithium, corticosteroids and other neuromodulators can suppress attacks during cluster periods (1). All standard medication treatments may be ineffective. Surgical treatment may be an option for medication non-responders, including deep brain (4) or occipital nerve stimulation (5). However, serious complications from brain surgery, including death, can occur (6). An Internet survey of 53 CH patients reported on claims that psilocybin is better at aborting acute attacks than either oxygen or sumatriptan and that LSD and psilocybin are both better at triggering and extending remission than standard drugs (7). However, due to hallucinogenicity and the absence of established medical indication, these drugs are criminalized and placed within the most restrictive Schedule I of the Controlled Substances Act, which sanctions only limited research use. Although the hallucinogenic properties of LSD and psilocybin are undesirable from both regulatory and patient safety perspectives, it was unclear to us at the outset whether a non-hallucinogenic analog could also provide meaningful relief to CH patients. To address the question of whether the CH relief associated with these two structurally diverse compounds is related to the mechanisms triggering intoxication, we decided to investigate the efficacy of a nonhallucinogenic analog of LSD. LSD’s hallucinogenic effects are completely lost when the double bond in the D ring is saturated and with substitution at R2 (e.g. by bromination in 2-bromo-LSD) (BOL-148) (8). BOL-148 has been studied in volunteers (up to 20mg per os) (9) and in patients suffering from vascular headaches but not, apparently, in patients with CH (9,10). These past studies concluded that BOL-148 is non-toxic and non-hallucinogenic. Only very mild side effects, if any, have been observed, when given in the dose range used in our project (30mg/kg/body weight) (9). No long-term behavioral or psychological effects from BOL-148 have been reported from past studies with more than 300 healthy, normal subjects (11), and 30mg BOL-148 administered daily over four to five weeks failed to alter active psychosis in chronically ill schizophrenic women (12).

Previous studies reported that respiratory feedback (RFB) aids in alleviating chronic pain. However, to date, this adjunct treatment has not been rigorously tested against non-contingent (placebo) feedback. Forty-two patients with chronic low back pain were randomized to either RFB or non-contingent RFB. Both groups performed a daily 30-min home training for 15 consecutive days. A respiratory associated relaxation index (RI) was measured. Pain levels and a somatosensory profile were assessed before and after intervention. Additionally, pain levels were assessed 3 months after the end of intervention. Secondary outcome parameters included daily functioning, psychopathology, and suggestibility. T-tests showed higher and significant pain reductions for RFB, compared to non-contingent RFB. Between-group comparisons reached no significance. However, changes were more pronounced in the RFB condition, which was also true for the course of the RI and the psychopathological scores. This is the first study using a non-contingent respiratory placebo feedback in a randomized, controlled design. Within this design previous positive findings of symptom reductions in patients treated with RFB could partially replicated. Nonetheless, tendencies suggest that contingent feedback patients compared to placebo patients profit more from RFB in the long run regarding reduction of chronic pain and psychological distress.

Background: In a previous study it has been shown that acupuncture activates the respiratory burst (RB) of neutrophils as measured by the differences to baseline of the mean channel number of fluorescence intensity (mfi) in volunteers. Since this result could have been affected by a placebo effect, a study has been designed that controls for the different facets of placebo mechanisms such as expectancy, suggestibility, and conditioning. Participants and Methods: 60 healthy volunteers were randomized either to acupuncture of the acupoint Large Intestine 11 (LI 11) (groups 1 and 2) or relaxation (group 3) twice a week for 4 weeks. Only acupuncture group 1 and the relaxation group were provided with the additional suggestion that the treatment may strengthen the immune system. Results: The repeated measurement analysis for differences of follow-ups to baseline showed significantly different treatment effects for neutrophils but not for monocytes (unprimed neutrophils: p = 0.004; neutrophils primed with TNF-alpha/FMLP or with FMLP only: p = 0.026 and p = 0.019, respectively) between groups. For both cell types post-hoc Dunnett’s t-tests using the relaxation group as control showed significantly stronger treatment effects for acupuncture group 1. Combining all priming procedures, the average increase in mfi for both cell types was about 30% greater in acupuncture group 1 than in the relaxation group. Plasma concentrations of pro-inflammatory cytokines only increased significantly in the acupuncture groups. Conclusion: Repetitive acupuncture increases the cytotoxicity of leukocytes in healthy volunteers, which might be intensified by a conditioning-expectation effect.