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T. Passie

Rediscovering MDMA (ecstasy): the role of the American chemist Alexander T. Shulgin

July 9, 2010 / Humanities & Art, MDMA, Papers, Pharmacology & Chemistry, 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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The non-hallucinogen 2-bromo-lysergic acid diethylamide as preventative treatment for cluster headache: An open, non-randomized case series

March 26, 2010 / Headache Pain and Neurological Disorders, LSD, Neuroscience, Papers, Pharmacology & Chemistry, Psychiatry & Medicine, Publications / By / , , ,

Introduction

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 non-hallucinogenic 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 20 mg per os) (9) and in patients suffering from vascular headaches but not, apparently, in patients with CH (9,10). These past studies [fusion_builder_container hundred_percent=”yes” overflow=”visible”][fusion_builder_row][fusion_builder_column type=”1_1″ background_position=”left top” background_color=”” border_size=”” border_color=”” border_style=”solid” spacing=”yes” background_image=”” background_repeat=”no-repeat” padding=”” margin_top=”0px” margin_bottom=”0px” class=”” id=”” animation_type=”” animation_speed=”0.3″ animation_direction=”left” hide_on_mobile=”no” center_content=”no” min_height=”none”][…]

Karst, M., Halpern, J. H., Bernateck, M., & Passie, T. (2010). The non-hallucinogen 2-bromo-lysergic acid diethylamide as preventative treatment for cluster headache: An open, non-randomized case series. Cephalalgia, 30(9), 1140-1144. https://dx.doi.org/10.1177/0333102410363490
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The Pharmacology of Lysergic Acid Diethylamide: A Review

November 11, 2008 / LSD, Papers, Psychology, Publications / By / , , , ,

Abstract

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.

Passie, T., Halpern, J. H.,  Stichtenoth, D. O., Emrich, H. M., & Hintzen, A. (2008). The Pharmacology of Lysergic Acid Diethylamide: A Review. CNS Neuroscience & Therapeutics, 14(4), 295–314. http://dx.doi.org/10.1111/j.1755-5949.2008.00059.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, Biology & Ethnobotany, Papers, Psychology, Publications / 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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Effects of different subanesthetic doses of (S)-ketamine on neuropsychology, psychopathology, and state of consciousness in man

May 12, 2005 / Ketamine, Papers, Psychology, Publications / By / , , , ,

Abstract

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 impair ment 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.

Passie, T., Karst, M., Wiese, B., Emrich, H. M., & Schneider, U. (2005). Effects of different subanesthetic doses of (S)-ketamine on neuropsychology, psychopathology, and state of consciousness in man. Neuropsychobiology, 51(4), 226-233. http://dx.doi.org/10.1159%2F000085724
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Ecstasy (MDMA) mimics the post-orgasmic state: impairment of sexual drive and function during acute MDMA-effects may be due to increased prolactin secretion

November 9, 2004 / MDMA, Neuroscience, Papers, Publications / By / , , , ,

Summary

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.

 

Passie, T., Hartmann, U., Schneider, U., Emrich, H. M., & Krüger, T. H. (2005). Ecstasy (MDMA) mimics the post-orgasmic state: impairment of sexual drive and function during acute MDMA-effects may be due to increased prolactin secretion. Medical hypotheses, 64(5), 899-903. https://dx.doi.org/10.1016/j.mehy.2004.11.044

 

Effects of different subanaesthetic doses of (S)-ketamine on psychopathology and binocular depth inversion in man

January 1, 2003 / Ketamine, Papers, Psychology, Psychotic Disorders, Publications / By / , , , , ,

Abstract

The role of the N-methyl-D-aspartate (NMDA) neurotransmitter system in relation to psychoses is not completely understood, but represent a challenge in neurobiological research. The psychotic states induced by NMDA antagonists such as phencyclidine and ketamine have been described as being most similar to schizophrenia and the NMDA system has been implicated in the pathogenesis of schizophrenia. Binocular depth inversion, an illusion of visual perception, has been shown to be impaired in psychotic and psychotomimetic states in healthy and schizophrenic subjects. In this study, pictures of natural and artificial objects were presented stereoscopically to 12 healthy male volunteers and depth perception assessed using an operationalized method. The effects of the psychotomimetic S-enantiomer of the anaesthetic ketamine in two different subanaesthetic doses were compared with those of a placebo. In spite of dose dependence and grave subjective and significant objective psychopathology, no significant impairment of binocular depth perception was found with (S)-ketamine. Implications related to memory function, perceptogenesis and ‘bottom-up’ processing in ketamine model psychosis and schizophrenia are discussed.

Passie, T., Karst, M., Borsutzky, M., Wiese, B., Emrich, H. M., & Schneider, U. (2003). Effects of different subanaesthetic doses of (S)-ketamine on psychopathology and binocular depth inversion in man. Journal of Psychopharmacology, 17(1), 51-56. http://dx.doi.org/10.1177/0269881103017001698
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The pharmacology of psilocybin

May 30, 2002 / Mushrooms / Psilocybin, Papers, Publications / By / , , ,

Abstract

Psilocybin (4-phosphoryloxy-N,N-dimethyltryptamin e) is the major psychoactive alkaloid of some species of mushrooms distributed worldwide. These mushrooms represent a growing problem regarding hallucinogenic drug abuse. Despite its experimental medical use in the 1960s, only very few pharmacological data about psilocybin were known until recently. Because of its still growing capacity for abuse and the widely dispersed data this review presents all the available pharmacological data about psilocybin.

Passie, T., Seifert, J., Schneider, U., & Emrich, H. M. (2002). The pharmacology of psilocybin. Addiction Biology, 7(4), 357-364. http://dx.doi.org/10.1080/1355621021000005937

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