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Psychotherapy

The safety and efficacy of ±3,4-methylenedioxymethamphetamineassisted psychotherapy in subjects with chronic, treatment-resistant posttraumatic stress disorder

July 19, 2010 / Anxiety disorders / PTSD, MDMA, Papers, Psychiatry, Psychology, Psychopharmacology, Psychotherapy, Publications, Safety / By / , , , ,

Abstract

Case reports indicate that psychiatrists administered 3,4-methylenedioxymethamphetamine (MDMA) as a catalyst to psychotherapy before recreational use of MDMA as ‘Ecstasy’ resulted in its criminalization in 1985. Over two decades later, this study is the first completed clinical trial evaluating MDMA as a therapeutic adjunct. Twenty patients with chronic posttraumatic stress disorder, refractory to both psychotherapy and psychopharmacology, were randomly assigned to psychotherapy with concomitant active drug (n¼12) or inactive placebo (n¼8) administered during two 8-h experimental psychotherapy sessions. Both groups received preparatory and follow-up non-drug psychotherapy. The primary outcome measure was the Clinician- Administered PTSD Scale, administered at baseline, 4 days after each experimental session, and 2 months after the second session. Neurocognitive testing, blood pressure, and temperature monitoring were performed. After 2-month follow-up, placebo subjects were offered the option to re-enroll in the experimental procedure with open-label MDMA. Decrease in Clinician-Administered PTSD Scale scores from baseline was significantly greater for the group that received MDMA than for the placebo group at all three time points after baseline. The rate of clinical response was 10/12 (83%) in the active treatment group versus 2/8 (25%) in the placebo group. There were no drug-related serious adverse events, adverse neurocognitive effects or clinically significant blood pressure increases. MDMA-assisted psychotherapy can be administered to posttraumatic stress disorder patients without evidence of harm, and it may be useful in patients refractory to other treatments.

Mithoefer, M. C., Wagner, M. T., Mithoefer, A. T., Jerome, L., & Doblin, R. (2010). The safety and efficacy of ±3,4-methylenedioxymethamphetamineassisted psychotherapy in subjects with chronic, treatment-resistant posttraumatic stress disorder: the first randomized controlled pilot study. Journal of Psychopharmacology, 25(4), 439-452. http://dx.doi.org/10.1177/0269881110378371
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Rediscovering MDMA (ecstasy): the role of the American chemist Alexander T. Shulgin

July 9, 2010 / Chemistry, History, MDMA, Other subjects, Papers, Psychotherapy, Publications / By / ,

Abstract

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.

Benzenhöfer, U., & Passie, T. (2010). Rediscovering MDMA (ecstasy): the role of the American chemist Alexander T. Shulgin. Addiction, 105(8), 1355–1361. http://dx.doi.org/10.1111/j.1360-0443.2010.02948.x
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How could MDMA (ecstasy) help anxiety disorders? A neurobiological rationale

March 9, 2009 / Anxiety disorders / PTSD, MDMA, Neuroscience, Papers, Psychiatry, Psychology, Psychopharmacology, Psychotherapy, Publications / By / ,

Abstract

Exposure therapy is known to be an effective treatment for anxiety disorders. Nevertheless, exposure is not used as much as it should be, and instead patients are often given supportive medications such as serotonin reuptake inhibitors (SSRIs) and benzodiazepines, which may even interfere with the extinction learning that is the aim of treatment. Given that randomized controlled trials are now investigating a few doses of ±3,4-methylenedioxymethamphetamine (MDMA, ‘ecstasy’) in combination with psychotherapy for treatment-resistant anxiety disorders, we would like to suggest the following three mechanisms for this potentially important new approach: 1) MDMA increases oxytocin levels, which may strengthen the therapeutic alliance; 2) MDMA increases ventromedial prefrontal activity and decreases amygdala activity, which may improve emotional regulation and decrease avoidance and 3) MDMA increases norepinephrine release and circulating cortisol levels, which may facilitate emotional engagement and enhance extinction of learned fear associations. Thus, MDMA has a combination of pharmacological effects that, in a therapeutic setting, could provide a balance of activating emotions while feeling safe and in control, as described in case reports of MDMA-augmented psychotherapy. Further clinical and preclinical studies of the therapeutic value of MDMA are indicated.

Johansen, P. Ø., & Krebs, T. S. (2009). How could MDMA (ecstasy) help anxiety disorders? A neurobiological rationale. Journal of Psychopharmacology, 23(4), 389-391. http://dx.doi.org/10.1177/0269881109102787
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Gaddum and LSD: the birth and growth of experimental and clinical neuropharmacology research on 5-HT in the UK

January 29, 2009 / Depression, LSD, Medicine, Neuroscience, Other subjects, Other substances, Papers, Psychopharmacology, Psychotherapy, Publications / By /

Abstract

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.

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., 10.1038/bjp.2008.207
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Serotonin-Related Psychedelic Drugs

November 5, 2008 / Cacti / Mescaline, LSD, Mushrooms / Psilocybin, Neuroscience, Papers, Psychiatry, Psychology, Psychopharmacology, Psychotherapy, Publications / By / , ,

Abstract

Serotonergic hallucinogens include the prototypical compounds such as mescaline, psilocybin, and LSD, representing the chemical classes of phenethylamines, tryptamines, and ergolines. Known as psychedelics, these compounds induce dramatic alterations of perception, affect, consciousness, and the experience of self. As first discovered in animal studies and recently confirmed in humans, the psychological effects of psychedelics are primarily attributable to the activation of the 5-HT2A subtype of serotonin receptors in brain. Research on psychedelic compounds has provided important insights into the neurobiology of consciousness and naturally occurring psychotic states and may lead to further advances in the development of psychiatric pharmacotherapeutics.

Geyer, M. A., Nichols, D. E., & Vollenweider, F. X. (2009). Serotonin-related psychedelic drugs. 10.1016/B978-008045046-9.01160-8
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The Phenomenology and Potential Religious Import of States of Consciousness Facilitated by Psilocybin

October 30, 2008 / Mushrooms / Psilocybin, Mystical experiences, Neuroscience, Papers, Personal development, Phenomenology, Psychiatry, Psychology, Psychopharmacology, Psychotherapy, Publications, Religious studies, Spirituality / By /

Abstract

Accompanying the resumption of human research with the entheogen (psychedelic drug), psilocybin, the range of states of consciousness reported during its action, including both nonmystical and mystical forms of experience, is surveyed and defined. The science and art of facilitating mystical experiences is discussed on the basis of research experience. The potential religious import of these states of consciousness is noted in terms of recognizing the reality of the spiritual, in better understanding the biochemistry of revelation, and in exploring the potentially positive contributions that mystical consciousness may effect in psychological treatment.

Richards, W. A. (2008). The Phenomenology and Potential Religious Import of States of Consciousness Facilitated by Psilocybin. Archive for the Psychology of Religion, 30, 189-199. http://dx.doi.org/10.1163/157361208X317196
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Ayahuasca and Spiritual Crisis: Liminality as Space for Personal Growth

September 16, 2008 / Anthropology, Ayahuasca, Mystical experiences, Papers, Personal development, Psychology, Psychosis, Psychotherapy, Publications, Spirituality / By / ,

Abstract

There is an increased controversy surrounding Westerners’ use of ayahuasca. One issue of importance is psychological resiliency of users and lack of screening by ayahuasca tourism groups in the Amazon. Given the powerful effects of ayahuasca coupled with lack of cultural support, Western users are at increased risk for psychological distress. Many Westerners who experience psychological distress following ayahuasca ceremonies report concurrently profound spiritual experiences. Because of this, it may be helpful to consider these episodes “spiritual emergencies,” or crises resulting from intense and transformative spiritual experiences. Although the author warns readers to avoid romantic comparisons of Western ayahuasca users to shamans, ethnographic data on indigenous shamanic initiates along with theory on liminality may be of some use to understand difficult experiences that accompany ayahuasca use. Given that psychotherapy is culturally sanctioned, therapists trained in treating spiritual crises can help Western ayahuasca users make meaning of their distress. Three case studies are offered as examples of individuals working through various sorts of crises following ayahuasca ceremonies.

Lewis, S. E. (2008). Ayahuasca and spiritual crisis: Liminality as Space for Personal Growth. Anthropology of Consciousness, 19(2), 109-133. https://dx.doi.org/10.1111/j.1556-3537.2008.00006.x
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Evidence of health and safety in American members of a religion who use a hallucinogenic sacrament

August 1, 2008 / Ayahuasca, Ethnobotany, Indigenous use, Papers, Personal development, Personality, Psychiatry, Psychology, Psychotherapy, Publications, Safety / By / , , , ,

Summary

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 benefi ts 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 benefi t, especially if subjects interviewed fully refl ect general membership. Further research is warranted with blinded raters, matched comparison groups, and other measures to overcome present study limitations.

Halpern, J. H., Sherwood, A. R., Passie, T., Blackwell, K. C., & Ruttenber, A. J. (2008). Evidence of health and safety in American members of a religion who use a hallucinogenic sacrament. Medical Science Monitor, 14(8), SR15-SR22. PMID: 18668010

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Land of the Living Sky with Diamonds: A Place for Radical Psychiatry?

October 1, 2007 / LSD, Other disciplines, Papers, Psychiatry, Psychotherapy, Publications / By /

Abstract

Dr. Humphry Osmond first published the term “psychedelic” in 1957 as a result of an extensive set of clinical investigations with d-lysergic acid diethylmide (LSD) that took place in Saskatchewan in the 1950s. In the post-World War Two period, Saskatchewan became an attractive destination for medical, and in this case psychiatric, researchers who wanted to pursue theoretical and practical investigations that challenged disciplinary boundaries and critically examined the relationship between medicine and the state. Partly as a result of Saskatchewan’s post-war political culture, the province became an intellectual sanctuary for medical experimentation that in some other contexts did not gain currency because it appeared too radical. This essay examines the way that psychedelic psychiatry emerged in that province and argues that the social, cultural and political environment in post-war Saskatchewan played a significant role in attracting researchers and supporting LSD research.

Dyck, E. (2007). Land of the living sky with diamonds: A place for radical psychiatry?. Journal of Canadian Studies/Revue d’études canadiennes, 41(3), 42-66.
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Safety, tolerability, and efficacy of psilocybin in 9 patients with obsessive-compulsive disorder

November 11, 2006 / Anxiety disorders / PTSD, Mushrooms / Psilocybin, Other subjects, Papers, Psychiatry, Psychology, Psychopharmacology, Psychotherapy, Publications, Safety / By / , , ,

Abstract

Background: Anecdotal reports suggest that psychedelic agents may relieve symptoms of obsessive-compulsive disorder (OCD). This modified double-blind study investigated the safety, tolerability, and clinical effects of psilocybin, a potent 5-HT(1A) and 5-HT(2A/2C) agonist, in patients with OCD.

Method: Nine subjects with DSM-IV-defined OCD and no other current major psychiatric disorder participated in up to 4 single-dose exposures to psilocybin in doses ranging from sub-hallucinogenic to frankly hallucinogenic. Low (100 microg/kg), medium (200 microg/kg), and high (300 microg/kg) doses were assigned in that order, and a very low dose (25 microg/kg) was inserted randomly and in double-blind fashion at any time after the first dose. Testing days were separated by at least 1 week. Each session was conducted over an 8-hour period in a controlled environment in an outpatient clinic; subjects were then transferred to a psychiatric inpatient unit for overnight observation. The Yale-Brown Obsessive Compulsive Scale (YBOCS) and a visual analog scale measuring overall obsessive-compulsive symptom severity were administered at 0, 4, 8, and 24 hours post-ingestion. The Hallucinogen Rating Scale was administered at 8 hours, and vital signs were recorded at 0, 1, 4, 8, and 24 hours after ingestion. The study was conducted from November 2001 to November 2004.

Results: Nine subjects were administered a total of 29 psilocybin doses. One subject experienced transient hypertension without relation to anxiety or somatic symptoms, but no other significant adverse effects were observed. Marked decreases in OCD symptoms of variable degrees were observed in all subjects during 1 or more of the testing sessions (23%-100% decrease in YBOCS score). Repeated-measures analysis of variance for all YBOCS values revealed a significant main effect of time on Wilks lambda (F = 9.86, df = 3,3; p = .046), but no significant effect of dose (F = 2.25, df = 3,3; p = .261) or interaction of time and dose (F = 0.923, df = 9,45; p = .515). Improvement generally lasted past the 24-hour timepoint.

Conclusion: In a controlled clinical environment, psilocybin was safely used in subjects with OCD and was associated with acute reductions in core OCD symptoms in several subjects.
Moreno, F. A., Wiegand, C. B., Taitano, E. K., & Delgado, P. L. (2006). Safety, tolerability, and efficacy of psilocybin in 9 patients with obsessive-compulsive disorder. Journal of Clinical Psychiatry, 67(11), 1735-1740.

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7 May - Psychedelics, Nature & Mental Health with Sam Gandy

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