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Human hallucinogen research: guidelines for safety

July 1, 2008 / Ayahuasca, DMT, Iboga / Ibogaine, Ketamine, LSD, MDMA, Mescaline / Cacti, Mushrooms / Psilocybin, Neuroscience, Papers, Psychiatry & Medicine, Psychology, Publications, Salvia / Salvinorin A / By / , ,

Abstract

There has recently been a renewal of human research with classical hallucinogens (psychedelics). This paper first briefly discusses the unique history of human hallucinogen research, and then reviews the risks of hallucinogen administration and safeguards for minimizing these risks. Although hallucinogens are relatively safe physiologically and are not considered drugs of dependence, their administration involves unique psychological risks. The most likely risk is overwhelming distress during drug action (‘bad trip’), which could lead to potentially dangerous behaviour such as leaving the study site. Less common are prolonged psychoses triggered by hallucinogens. Safeguards against these risks include the exclusion of volunteers with personal or family history of psychotic disorders or other severe psychiatric disorders, establishing trust and rapport between session monitors and volunteer before the session, careful volunteer preparation, a safe physical session environment and interpersonal support from at least two study monitors during the session. Investigators should probe for the relatively rare hallucinogen persisting perception disorder in follow-up contact. Persisting adverse reactions are rare when research is conducted along these guidelines. Incautious research may jeopardize participant safety and future research. However, carefully conducted research may inform the treatment of psychiatric disorders, and may lead to advances in basic science.

Johnson, M. W., Richards, W. A., & Griffiths, R. R. (2008). Human hallucinogen research: guidelines for safety.  Journal of Psychopharmacology, 22(6), 603–620. http://dx.doi.org/10.1177/0269881108093587
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'Hybrid' benzofuran-benzopyran congeners as rigid analogs of hallucinogenic phenethylamines

June 1, 2008 / LSD, Papers, Pharmacology & Chemistry, Publications / By / , , , , ,

Abstract

Phenylalkylamines that possess conformationally rigidified furanyl moieties in place of alkoxy arene ring substituents have been shown previously to possess the highest affinities and agonist functional potencies at the serotonin 5-HT2A receptor among this chemical class. Further, affinity declines when both furanyl rings are expanded to the larger dipyranyl ring system. The present paper reports the synthesis and pharmacological evaluation of a series of ‘hybrid’ benzofuranyl–benzopyranyl phenylalkylamines to probe further the sizes of the binding pockets within the serotonin 5-HT2A agonist binding site. Thus, 4(a–b), 5(a–b), and 6 were prepared as homologs of the parent compound, 8-bromo-1-(2,3,6,7-tetrahydrobenzo[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”][1,2-b:4,5-b0]difuran-4-yl)- 2-aminopropane 2, and their affinity, functional potency, and intrinsic activity were assessed using cells stably expressing the rat 5-HT2A receptor. The behavioral pharmacology of these new analogs was also evaluated in the two-lever drug discrimination paradigm. Although all of the hybrid isomers had similar, nanomolar range receptor affinities, those with the smaller furanyl ring at the arene 2-position (4a–b) displayed a 4- to 15-fold greater functional potency than those with the larger pyranyl ring at that position (5a–b). When the furan ring of the more potent agonist 4b was aromatized to give 6, a receptor affinity similar to the parent difuranyl compound 2 was attained, along with a functional potency equivalent to 2, 4a, and 4b. In drug discrimination experiments using rats trained to discriminate LSD from saline, 4b was more than two times more potent than 5b, with the latter having a potency similar to the classic hallucinogenic amphetamine 1 (DOB).

Schultz, D. M.,  Prescher, J. A., Kidd, S., Marona-Lewicka, D., Nichols, D. E., & Montea, A. (2008). ‘Hybrid’ benzofuran-benzopyran congeners as rigid analogs of hallucinogenic phenethylamines. Bioorganic & Medicinal Chemistry, 16(11), 6242–6251. http://dx.doi.org/10.1016/j.bmc.2008.04.030
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[Hallucinogen-induced psychological disorders]

June 1, 2008 / LSD, Mushrooms / Psilocybin, Neuroscience, Papers, Psychology, Psychotic Disorders, Publications / By / , , ,

Abstract

OBJECTIVE:

The purpose of this article is to provide an overview of the current research on hallucinogen induced psychiatric disorders. In addition to LSD and psilocybin hallucinogens of biologic origin are increasingly used by adolescents and young adults.

METHODS:

Relevant literature and related articles were identified by means of a computerized MEDLINE search including the years 1997 – 2007. As keywords “hallucinogen induced psychosis”, “hallucinogen induced flashback”, “hallucinogen persisting perception disorder (HPPD)” were used. Finally, 64 journal articles and books out of 103 were included in the review.

RESULTS:

Acute psychotic syndromes in adolescents are rarely due to intoxications with hallucinogenic drugs. However, clinical relevance of flashback phenomena as post-hallucinogenic psychiatric disorder has to be disputed. Because of the high popularity of biogenic hallucinogens and LSD knowledge of intoxications and resulting psychiatric disorders as well as medical complications and therapeutical approaches are clinically important. Especially intoxications with drugs of herbal origin like tropanalcaloids play an important role in emergency situations.

Hermle, L., Kovar, K. A., Hewer, W., & Ruchsow, M. (2008). [Hallucinogen-induced psychological disorders]. Fortschritte der Neurologie-Psychiatrie, 76(6), 334-342. http://dx.doi.org/10.1055/s-2008-1038191
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Identification of N,N-dimethyltryptamine and beta-carbolines in psychotropic ayahuasca beverage

May 27, 2008 / Ayahuasca, Biology & Ethnobotany, Papers, Pharmacology & Chemistry, Publications / By / , , , ,

Abstract

Recently many people have shown great interest in traditional indigenous practices and popular medicine, involving the ingestion of natural psychotropic drugs. We received a request to analyze and determine the nature of a dark green liquid with a dark brown plant sediment, which the police had seized at an airport and inside the home of a person belonging to the ‘Santo Daime’ religious movement. Gas chromatography/mass spectrometry analysis of the extract identified N,N-dimethyltryptamine, a potent hallucinogen, and the β-carboline alkaloids harmine and harmaline, revealing monoamine oxidase A-inhibiting properties. These substances are typical components of Ayahuasca, a South American psychotropic beverage obtained by boiling the bark of the liana Banisteriopsis caapi together with the leaves of various admixture plants, principally Psychotria viridis.

Gambelunghe, C., Aroni, K., Rossi, R., Moretti, L., & Bacci, M. (2008). Identification of N, N‐dimethyltryptamine and β‐carbolines in psychotropic ayahuasca beverage. Biomedical Chromatography, 22(10), 1056-1059. 10.1002/bmc.1023
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Selective 5-HT2A agonist hallucinogens: A review of pharmacological interaction and corollary perceptual effects

May 23, 2008 / DMT, LSD, Mushrooms / Psilocybin, Neuroscience, Papers, Psychology, Publications / By /

Abstract

The most potent tryptamine hallucinogens – such as DMT, psilocybin, and LSD – are all active at the 5-HT2A receptor subtype and all produce similar visual perceptual results that are immediately recognizable as uniquely psychedelic. Although it is widely accepted that selective serotonin receptor subtype 2A agonism is directly responsible for producing the distinct hallucinations seen on a psychedelic trip, no single theory has yet explained why this is so. Utilizing what we know about psychedelic tryptamine receptor interaction, sensory processing circuits in the neocortex, and EEG scans of psychedelics in action, this review will propose a novel multi-state theory of psychedelic action which invokes a variety of neural processing mechanisms, including phase-coupled neural oscillators; network excitation, disinhibition, and destabilization; recurrent feedback excitation; and neural circuit spike synchrony and brainwave cohesion to close the knowledge gap between the pharmaceutical interactions of selective 5-HT2A hallucinogens, their direct effects on perception and consciousness at varying dose ranges, and their potential long-term adverse effects.

Kent, J. (2008). Selective 5-HT2A agonist hallucinogens: A review of pharmacological interaction and corollary perceptual effects. Beta Review.

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Effects of varied doses of psilocybin on time interval reproduction in human subjects

April 11, 2008 / Mushrooms / Psilocybin, Papers, Psychology, Publications / By / , , ,

Abstract

Action of a hallucinogenic substance, psilocybin, on internal time representation was investigated in two double-blind, placebo-controlled studies: Experiment 1 with 12 subjects and graded doses, and Experiment 2 with 9 subjects and a very low dose. The task consisted in repeated reproductions of time intervals in the range from 1.5 to 5 s. The effects were assessed by parameter κκ of the ‘dual klepsydra’ model of internal time representation, fitted to individual response data and intra-individually normalized with respect to initial values. The estimates View the MathML sourceκˆ were in the same order of magnitude as in earlier studies. In both experiments, κκ was significantly increased by psilocybin at 90 min from the drug intake, indicating a higher loss rate of the internal duration representation. These findings are tentatively linked to qualitative alterations of subjective time in altered states of consciousness.

Wackermann, J., Wittmann, M., Hasler, F., & Vollenweider, F. X. (2008). Effects of varied doses of psilocybin on time interval reproduction in human subjects. Neuroscience letters, 435(1), 51-55. https://dx.doi.org/10.1016/j.neulet.2008.02.006
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The correlation between ketamine and posttraumatic stress disorder in burned service members

February 22, 2008 / Anxiety Disorders / PTSD, Ketamine, Papers, Psychology, Publications / By / , , , ,

Abstract

BACKGROUND:

Predisposing factors for posttraumatic stress disorder (PTSD) include experiencing a traumatic event, threat of injury or death, and untreated pain. Ketamine, an anesthetic, is used at low doses as part of a multimodal anesthetic regimen. However, since ketamine is associated with psychosomatic effects, there is a concern that ketamine may increase the risk of developing PTSD. This study investigated the prevalence of PTSD in Operation Iraqi Freedom/Operation Enduring Freedom (OIF/OEF) service members who were treated for burns in a military treatment center.

METHODS:

The PTSD Checklist-Military (PCL-M) is a 17-question screening tool for PTSD used by the military. A score of 44 or higher is a positive screen for PTSD. The charts of all OIF/OEF soldiers with burns who completed the PCL-M screening tool (2002-2007) were reviewed to determine the number of surgeries received, the anesthetic regime used, including amounts given, the total body surface area burned, and injury severity score. Morphine equivalent units were calculated using standard dosage conversion factors.

RESULTS:

The prevalence of PTSD in patients receiving ketamine during their operation(s) was compared with patients not receiving ketamine. Of the 25,000 soldiers injured in OIF/OEF, United States Army Institute of Surgical Research received 603 burned casualties, of which 241 completed the PCL-M. Of those, 147 soldiers underwent at least one operation. Among 119 patients who received ketamine during surgery and 28 who did not; the prevalence of PTSD was 27% (32 of 119) versus 46% (13 of 28), respectively (p = 0.044).

CONCLUSIONS:

Contrary to expectations, patients receiving perioperative ketamine had a lower prevalence of PTSD than soldiers receiving no ketamine during their surgeries despite having larger burns, higher injury severity score, undergoing more operations, and spending more time in the ICU.

McGhee, L. L., Maani, C. V., Garza, T. H., Gaylord, K. M., & Black, I. H. (2008). The correlation between ketamine and posttraumatic stress disorder in burned service members. Journal of Trauma and Acute Care Surgery, 64(2), S195-S199. https://dx.doi.org/10.1097/TA.0b013e318160ba1d
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The behavioral pharmacology of hallucinogens

January 1, 2008 / DMT, LSD, MDMA, Mescaline / Cacti, Mushrooms / Psilocybin, Papers, Pharmacology & Chemistry, Publications / By / , ,

Abstract

Until very recently, comparatively few scientists were studying hallucinogenic drugs. Nevertheless, selective antagonists are available for relevant serotonergic receptors, the majority of which have now been cloned, allowing for reasonably thorough pharmacological investigation. Animal models sensitive to the behavioral effects of the hallucinogens have been established and exploited. Sophisticated genetic techniques have enabled the development of mutant mice, which have proven useful in the study of hallucinogens. The capacity to study post-receptor signaling events has lead to the proposal of a plausible mechanism of action for these compounds. The tools currently available to study the hallucinogens are thus more plentiful and scientifically advanced than were those accessible to earlier researchers studying the opioids, benzodiazepines, cholinergics, or other centrally active compounds. The behavioral pharmacology of phenethylamine, tryptamine, and ergoline hallucinogens are described in this review, paying particular attention to important structure activity relationships which have emerged, receptors involved in their various actions, effects on conditioned and unconditioned behaviors, and in some cases, human psychopharmacology. As clinical interest in the therapeutic potential of these compounds is once again beginning to emerge, it is important to recognize the wealth of data derived from controlled preclinical studies on these compounds.

Fantegrossi, W. E.,  Murnane, K. S., & Reissig, C. J. (2008). The behavioral pharmacology of hallucinogens. Biochemical Pharmacology 75(1), 17–33. http://dx.doi.org/10.1016/j.bcp.2007.07.018
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Ayahuasca and Anthropology: Amazonian Shamanism & Western Science

January 13, 2022 / Uncategorized / By

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In this lecture at the University of Amsterdam on Monday December 17th 2007, Arno Adelaars introduced ayahuasca to those unfamiliar with the substance, after which Jeremy Narby filled the rest of the time. He spoke about ayahuasca and his experiences with the Ashaninca in the Peruvian Amazon.

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Comparative potencies of MDMA analogues as inhibitors of [3H]noradrenaline and [3H]5-HT transport in mammalian cell lines

December 1, 2007 / MDMA, Papers, Pharmacology & Chemistry, Publications / By / , , , , ,

Abstract

Background and purpose:Illegal ‘ecstasy’ tablets frequently contain 3,4-methylenedioxymethamphetamine (MDMA)-like compounds of unknown pharmacological activity. Since monoamine transporters are one of the primary targets of MDMA action in the brain, a number of MDMA analogues have been tested for their ability to inhibit [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”][3H]noradrenaline uptake into rat PC12 cells expressing the noradrenaline transporter (NET) and [3H]5-HT uptake into HEK293 cells stably transfected with the 5-HT transporter (SERT).

Experimental approach:Concentration–response curves for the following compounds at both NET and SERT were determined under saturating substrate conditions: 4-hydroxy-3-methoxyamphetamine (HMA), 4-hydroxy 3-methoxymethamphetamine (HMMA), 3,4-methylenedioxy-N-hydroxyamphetamine (MDOH), 2,5-dimethoxy-4-bromophenylethylamine (2CB), 3,4-dimethoxymethamphetamine (DMMA), 3,4-methylenedioxyphenyl-2-butanamine (BDB), 3,4-methylenedioxyphenyl- N-methyl-2-butanamine (MBDB) and 2,3-methylenedioxymethamphetamine (2,3-MDMA).

Key results: 2,3-MDMA was significantly less potent than MDMA at SERT, but equipotent with MDMA at NET. 2CB and BDB were both significantly less potent than MDMA at NET, but equipotent with MDMA at SERT. MBDB, DMMA, MDOH and the MDMA metabolites HMA and HMMA, were all significantly less potent than MDMA at both NET and SERT.

Conclusions and implications: This study provides an important insight into the structural requirements of MDMA analogue affinity at both NET and SERT. It is anticipated that these results will facilitate understanding of the likely pharmacological actions of structural analogues of MDMA.

Montgomery, T., Buon, C., Eibauer, S., Guiry, P. J., Keenan, A.K., & McBean, G. J. (2007). Comparative potencies of MDMA analogues as inhibitors of [3H]noradrenaline and [3H]5-HT transport in mammalian cell lines. British Journal of Pharmacology, 152(7), 1121–1130. http://dx.doi.org/10.1038/sj.bjp.0707473
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