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In Memoriam Alexander ‘Sasha’ Shulgin

/ MDMA, Pharmacology & Chemistry /

With great sadness, the OPEN foundation would like to acknowledge the death of maverick chemist Alexander “Sasha” Shulgin, who passed away on June 2nd. Dubbed “the godfather of Ecstasy,” Shulgin was credited with introducing MDMA to psychologists in the late 70’s, years before the drug hit the global dance scene.

However MDMA was only one of hundreds of chemicals Shulgin synthesized during his lengthy career. After earning his biochemistry degree from UC Berkeley in 1954, he worked briefly as research director at BioRad Laboratories before becoming a senior research chemist at Dow Chemical Company, where he synthesized the first biodegradable insecticide, Zectran.

Because Shulgin made Dow a sizeable profit, he was granted the freedom to create and patent new drugs. He chose psychedelics. In the late 1950s, Shulgin experimented with mescaline, which he wrote revealed “that our entire universe is contained in the mind and spirit.” But his interest in pharmacology was sparked years earlier. While in the Navy as a teenager, he got a shot of morphine for an injury, making him wonder how drugs altered consciousness. This passion for understanding the human mind and how to unlock its potential—chemically, of course—would mark his career.

In 1966, Shulgin left Dow Chemical to freelance as a consultant and for the following decades worked from his backyard lab in Berkeley, California. In 1976, he heard about MDMA, which was first synthesized at Merck in 1912 as an unimportant precursor in a new synthesis for haemostatic substances and subsequently shelved. He went on to synthesize it, and discovered it was a powerful empathogen, “with emotional and sensual overtones.” He then introduced it to a therapist friend and word spread quickly both inside and outside the therapeutic community. Without MDMA, the dance music scene of the last 30 years would have looked entirely different.

Shulgin was a fixture in the psychedelic subculture that believed in better living through chemistry. He contributed a rational, scientific perspective to the field, coupled with enthusiasm for thorough self-experimentation.

When interviewed about the abuse potential of MDMA, which became a scheduled drug in 1985, Shulgin was quoted as saying it was “as real as the abuse potential of anything that gives pleasure and satisfaction. This applies to MDMA as much as it does to skydiving, mountain climbing and skiing.”

Shulgin died of several health complications after years of poor health, and had recently been diagnosed with terminal liver cancer. He was 88. His wife, Ann Shulgin, with whom he shared thousands of psychedelic experiences, survives him.

In Memoriam Alexander ‘Sasha’ Shulgin Read More »

Autism and LSD-25 – Freeing the Most Imprisoned Minds?

/ LSD /

In the early sixties, a number of controversial clinical investigations were published involving the administration of LSD-25 (lysergic acid diethylamide) to young children said to suffer from severe forms of autism, or childhood-onset schizophrenia (COS), which were then regarded as closely related [1]. The reason for conducting the studies with young children was the supposed similarity between autism and COS. Prompted by the apparent results of studies conducted with LSD-25 and adult mute catatonic patients by Cholden, Kurland, and Savage (1955), hypotheses were constructed to research a possible therapeutic utility. “The goal in these therapeutic efforts”, said Bender in an article published in Recent Advances in Biological Psychiatry (1962), “has been to modify the secondary symptomatology associated with retarded, regressed, and disturbed behavior of the children”. The larger part of the children treated with LSD in these studies were between six and ten years old and completely unresponsive to all other forms of treatment. That the children couldn’t be treated by other means served, in part, for the justification for using a powerful psychoactive substance in child experiments. Surely this decision would have been criticized by the ethical commission today.

A pharmacological intervention by means of LSD was said to “nudge the lagging maturation” (Bender, 1962) into a (somewhat) normal developmental pattern. How exactly the administration of LSD would accomplish the “freeing of the most imprisoned minds” was still unknown (Mogar & Aldrich, 1969). LSD was supposed to achieve success through “breaking through the autistic defense” (Bender, 1963), and in this way be exceptionally helpful in “areas which are closely related to the process of psychotherapy” (Simmons et al., 1966). Some believed LSD was especially useful at helping patients to “unblock” repressed subconscious material through other psychotherapeutic methods (Cohen, 1959). Therapists took LSD to establish a connection with the experience of schizophrenia. “During the ‘model psychosis’ phase of LSD research when the psychedelic state was considered a chemically-induced schizophrenia”, says pioneer LSD researcher Stanislav Grof (1980), “LSD sessions were recommended as reversible journeys into the experiential world of psychotics which had a unique didactic significance”.

Some researchers, like Freedman et al. (1963), studied LSD for its supposed psychotomimetic (psychotogenic) properties, meaning that the drug mimics the symptoms of psychosis, including delusions and/or delirium, as opposed to merely hallucinations (Sewell et al., 2009). An exacerbation of ‘typical’ symptoms meant an opportunity for studying the (child)schizophrenic condition. Other researchers (Bender et al., 1963; Rolo, et al., 1965) considered the neurological mechanism behind the effect of LSD, which in that time was still highly obscure, as more important than its role as facilitator of the therapeutic process. For instance, LSD attracted theoretical interest as a serotonin inhibitor and an autonomic nervous system stimulant. Bender et al. (1963) concluded that “LSD-25 given daily in oral doses of 100 mcg [2] to pre-puberty autistic schizophrenic children appears to be an effective autonomic and central nervous system stimulant”, and that these changes “appear to be chronic with continuous administration of the drug”. Continuous administration consisted of daily administration over prolonged periods of time, varying from days to several weeks . The most persistent effects of LSD-25 therapy that were published included improved speech behavior, increased emotional responsiveness, positive mood (laughter) and a decrease of compulsions.

But alas, however interesting and attractive these results seemed to be — the evidence didn’t stick. Today studies into the relationship of LSD and autism aren’t being conducted and the results that were produced are regarded as highly controversial, if not completely repudiated. This was in part because, in retrospect, the studies were greatly flawed. The researchers seemed to have brushed over the conceptual controversy too quickly by choosing “not to deal with the controversial issues concerning the definitions and etiological factors of either childhood schizophrenia (1) or the autistic reaction pattern (2)” (Bender et al., 1962). The debate about the correct place of (childhood) autism within the DSM (Diagnostic and Statistical Manual of Mental Disorders) remains problematic to this day (DSM-V), but autism has long been divorced from the umbrella of schizophrenia. Although both disorders share clinical features, clinical psychologists and psychiatrists regard autism to be a separate diagnostic ‘entity’ from schizophrenia. Because LSD was used as a drug for “intensifying pre-existing symptomology” of schizophrenia (Bender et al., 1962), a conceptual detachment from autism would have disturbed the foundation of the results.

Even if the researchers had chosen to ‘deal with the controversy’, in hindsight, sampling would have still ended up being very problematic. The children treated were demographically varied and covered a broad age range. Conflicting significance is given to the relationship between age and drug response, but Bender noted that “in contrast to pre- adolescents, younger children manifest consistently different reactions” (1962). In contrast, Fisher and Castile concluded that “older children were better candidates for psychedelic therapy because verbal communication was possible and also because they tended to be less withdrawn, more schizophrenic than autistic, and displayed more blatant symptomology” (Mogar & Aldrich, 1969). In addition to age, also the symptoms of treated children were heterogeneous and weren’t corrected for severity. There was no randomization, and most studies suffered from fluctuating frequency of administration and dosage. Lastly, the set and setting of the experiments varied strongly.

Although the studies conducted in the sixties had major flaws from an experimental point of view and therefore didn’t hold up to scientific scrutiny, Mogar and Aldrich argue in an article published in Behavioral Neuropsychiatry (1969) that the results considered as a whole do point to a utility of administering LSD to autistic children. “The significance of seemingly contradictory results”, say Mogar and Aldrich, “has often been obscured by the persistent search for static, ‘drug-specific’ reactions to LSD”. This is an interesting point; despite that the results don’t indicate significance in an experimental sense, there may still be a therapeutic utility. Mogar and Aldrich report that the greatest therapeutic benefit was related to “(a) the degree of active therapist involvement with the patient; (b) an opportunity to experience meaningful objects and interpersonal activities; and (c) congenial settings that were reasonably free of artificiality, experimental or medical restrictions, and mechanically administered procedures” (1969). In practice clinical therapy is usually far removed from theory. It could be that testing LSD, itself being a highly unpredictable drug, in combination with the therapy dynamic is too hard to substantiate. Mogar and Aldrich conclude that “the administration of LSD is inextricably embedded in a larger psychosocial process which should be optimized in accordance with particular treatment goals”.

Considering the recent growth of interest into this area of research, these older and rather obscure studies deserve to be excavated from the psychedelic research literature. Researchers at LA BioMed (Los Angeles Biomedical Research Institute) are now constructing a study which is said to test the already established anecdotal therapeutic relationship between MDMA (3,4-methylenedioxy-N-methylamphetamine) and autism in adults. The study is the latest in an expanding program of research into the therapeutic use of MDMA funded by the nonprofit Multidisciplinary Association for Psychedelic Studies (MAPS). “This new study will give us a chance”, says Charles Grob head researcher at LA BioMed (2014), “to determine the actual effects of differing dosages of medication that we know for certain is pure MDMA on adults on the autism spectrum. If the results of this research warrant further investigation, data from this study will be used to design additional clinical trials”. Now that the limitations for research into the psychedelic experience and its therapeutic effects are being removed and LSD is once again an object of study, these previously published results could serve for the production of new hypotheses.

 
[1] See (Abramson, 1960; Bender, et al., 1962; Bender, et al., 1963; Fisher & Castile, 1963; Freedman, et al., 1962; Rolo, et al., 1965; Simmons, et al., 1966).
[2] A common psychedelic dosage of LSD ranges from 100 to 200 mcg, a strong dose being 200 to 600 mcg.
 
References
Abramson, H.A. (Ed.) (1960). The Use of LSD in Psychotherapy. New York: Josiah Macy Foundation.
Bender, L., Faretra, G., & Cobrinik, L. (1963). LSD and UM-L treatment of hospitalized disturbed children. Recent Advances in Biological Psychiatry, 5, 84-92.
Bender, L., Goldschmidt, L., & Sankar, S.D.V. (1962). Treatment of autistic schizophrenic children with LSD-25 and UML-491. Recent Advances in Biological Psychiatry, 4, 170-177.
Cholden, L., Kurland, A., & Savage, C. (1955). Clinical reactions and tolerance to LSD in chronic schizophrenia. Journal of Nervous and Mental Disease, 122, 211-216.
Cohen, S., & Eisner, B. G. (1959). Use of lysergic acid diethylamide in a psychotherapeutic setting. AMA Archives of Neurology & Psychiatry, 81(5), 615-619.
Freedman, A.M., Ebin, E.V., & Wilson, E.A. (1962). Autistic schizophrenic children: An experiment in the use of d-lysergic acid diethylamide (LSD-25). Archives of General Psychiatry, 6, 203-213.
Gettys, T. (2014). MDMA Helps Reduce Social Anxiety for Autistic Adults, and Researchers Want to Find Out How. MAPS. Retrieved at: http://www.maps.org/media/view/mdma_helps_reduce_social_anxiety_for_autistic_adults_and_researchers_w/
Grof, S. (1980). LSD Psychotherapy. California: Hunter House Publishers.
Mogar, E. R., & Aldrich, W. R. (1969). The Use of Psychedelic Agents with Autistic Schizophrenic Children. Behavioral Neuropsychiatry, 1(8), 44-50.
Rolo, A., Krinsky. L.W., Abramson, H.A., & Goldfarb, L. (1965). Preliminary method for study of LSD with children. International Journal of Neuropsychiatry, 1, 552-555.
Sewell, R. A., Ranganathan, M., & D’Souza, D. C. (2009). Cannabinoids and psychosis. International Review of Psychiatry, 21(2), 152-162.
Simmons, J.Q., Leiken, SoJ., Lovaas, Q.I., Schaffer, B., & Perloff, B. (1966). Modification of autistic behavior with LSD-25. The American Journal of Psychiatry, 122, 1201-1211.

Autism and LSD-25 – Freeing the Most Imprisoned Minds? Read More »

Autisme en LSD-25 – Het Bevrijden van de Meest Gevangen Geesten?

/ Autism Spectrum Disorder, LSD, Psychiatry & Medicine, Scientific Discipline, Substance, Therapeutic Application /

In het begin van de jaren zestig zijn er een aantal controversiële klinische studies gepubliceerd waarin jonge kinderen met een autisme en/of ‘childhood-onset schizophrenia’ (COS) [1] diagnose LSD-25 (Lysergeenzuurdi-ethylamide) kregen toegediend. De reden dat deze studies werden uitgevoerd bij jonge kinderen was de veronderstelde gelijkenis van autisme en COS. Eerdere resultaten van onderzoek met LSD bij volwassen catatonische patiënten, gepubliceerd in Journal of Nervous and Mental Disease door Cholden, Kurland en Savage (1955), dienden als inspiratie voor dit onderzoek. “The goal in these therapeutic efforts”, schreef Bender in een artikel gepubliceerd in Recent Advances in Biological Psychiatry (1962), “has been to modify the secondary symptomatology associated with retarded, regressed, and disturbed behavior of the children”. Het grootste gedeelte van de kinderen in deze studies was tussen de zes en tien jaar oud en reageerde niet op andere vormen van therapie. Dat de kinderen niet behandeld konden worden rechtvaardigde volgens de onderzoekers het gebruik van sterke psychoactieve stoffen. Dergelijk onderzoek zou tegenwoordig uiteraard niet zomaar door de ethische commissie worden geaccepteerd.

Een farmacologische interventie door middel van LSD zou de vertraagde ontwikkeling veranderen naar een (enigszins) normaal ontwikkelingspatroon (Bender, 1962). Hoe het toedienen van LSD zou kunnen resulteren in “het bevrijden van de meest gevangen geesten” was echter nog onbekend (Mogar & Aldrich, 1969). LSD zou succesvol kunnen worden ingezet bij de behandeling van autisme vanwege het vermogen “door de autistische verdediging heen te breken” (Bender, 1963), en daarom bijzonder nuttig kunnen zijn in gebieden “closely related to the process of psychotherapy” (Simmons et al., 1966). Sommigen geloofden dat LSD bijzonder bruikbaar was om patiënten te helpen onderdrukt subbewust materiaal te “deblokkeren” in combinatie met andere psychotherapeutische methoden (Cohen, 1959). Ook waren er therapeuten die zelf LSD namen om een diepere bewustwording van de schizofrene ervaring te krijgen. “During the ‘model psychosis’ phase of LSD research when the psychedelic state was considered a chemically-induced schizophrenia”, zegt pionier LSD onderzoeker Stanislav Grof (1980), “LSD sessions were recommended as reversible journeys into the experiential world of psychotics which had a unique didactic significance”.

Sommige onderzoekers, zoals Freedman et al. (1963), onderzochten LSD vanwege de zogenaamde psychotomimetische eigenschappen, waarmee wordt bedoeld dat het middel symptomen van een psychose na zou bootsen, inclusief wanen en delierachtige verschijnselen, in plaats van alleen hallucinaties op te wekken (Sewell et al., 2009). Een versterking van ‘typische’ symptomen betekende de mogelijkheid om de (kinder)schizofrene conditie te bestuderen en mogelijk een therapeutische interventie te ontwikkelen. Andere onderzoekers (Bender et al., 1963; Rolo, et al., 1965) beschouwden de neurologische mechanismen achter de effecten van LSD, die toen nog zeer obscuur waren, als belangrijker dan de rol als facilitator van het therapeutische proces. LSD wekte bijvoorbeeld theoretische interesse omdat het serotonineactiviteit zou kunnen remmen en het autonome zenuwstelsel zou stimuleren. Bender et al. (1963) concludeerden dat “het toedienen van dagelijkse orale doseringen van 100 mcg [2] LSD-25 aan prepuberale autistische schizofrene kinderen effectief lijkt te zijn als een stimulant van het autonome en centrale zenuwstelsel”, en dat deze veranderingen “chronisch lijken te zijn bij een continue toediening van het middel”. Continue toediening bestond uit het dagelijks toedienen, variërend van enkele dagen tot een paar weken. Tot de meest robuuste effecten die werden gepubliceerd behoren een verbeterde spraak, verhoogde emotionele responsiviteit, positievere stemming (veel lachen) en een vermindering van compulsief gedrag.

Maar helaas, hoe interessant en aantrekkelijk deze resultaten ook leken te zijn – het bewijs was niet sterk genoeg. Tegenwoordig zijn er geen studies naar de relatie tussen LSD en autisme en de resultaten van deze eerdere studies worden als zeer controversieel of volledig achterhaald beschouwd. Dit komt gedeeltelijk, achteraf gezien, doordat de studies zeer grote tekortkomingen hadden. De onderzoekers gingen geheel voorbij aan de conceptuele controverse omtrent de definitie van autisme en/of (kinder)schizofrenie (Bender et al., 1962). Het debat over de correcte plaats van autisme binnen de DSM (Diagnostic and Statistical Manual of Mental Disorders) blijft tot op de dag van vandaag problematisch (DSM-V), maar autisme is al lang gescheiden van de psychotische stoornissen. Hoewel beide soorten stoornissen klinische eigenschappen delen beschouwen klinisch psychologen en psychiaters ze tegenwoordig als aparte diagnostische entiteiten. Omdat LSD onder andere werd gebruikt als een versterker van reeds bestaande symptomatologie van schizofrenie (Bender et al., 1962), zou een conceptuele scheiding tussen beide stoornissen de fundering van de resultaten hebben verzwakt.

Zelfs al hadden de onderzoekers gekozen om wel in te gaan op deze controverse, dan was de validiteit van de gebruikte steekproeven in de meeste onderzoeken achteraf gezien zeer problematisch geweest. De kinderen in de onderzoeken waren demografisch en wat leeftijd betreft erg gevarieerd. Niet alle onderzoekers waren het eens over de relatie tussen leeftijd en reactie op het middel, maar Bender stelde dat in tegenstelling tot preadolescenten, jongere kinderen consistent verschillende reacties vertoonden (1962). “Older children”, concludeerden Fisher en Castile daarentegen, “were better candidates for psychedelic therapy because verbal communication was possible and also because they tended to be less withdrawn, more schizophrenic than autistic, and displayed more blatant symptomology” (Mogar & Aldrich, 1969). Daarbij komt dat de symptomen van de behandelde kinderen heterogeen waren en dat er niet werd gecorrigeerd voor de ernst van de symptomen. Er was geen sprake van randomisering en in de meeste studies was er sprake van fluctuerende doseringen en frequentie van toediening. Ten slotte varieerde de set en setting van de experimenten sterk.

Hoewel de studies die in de jaren zestig verricht zijn belangrijke gebreken hadden vanuit een experimenteel oogpunt, beargumenteren Mogar en Aldrich in een artikel dat gepubliceerd is in Behavioral Neuropsychiatry (1969) dat de resultaten, als geheel bekeken, wel aanwijzingen bieden om de potentie van LSD bij de behandeling van autisme nader te onderzoeken. “The significance of seemingly contradictory results”, zeggen Mogar and Aldrich, “has often been obscured by the persistent search for static, ‘drug-specific’ reactions to LSD”. Dit is een interessant punt; ondanks dat de resultaten niet significant zijn in experimentele termen, is er wellicht wel een therapeutisch potentieel. Mogar en Aldrich rapporteren dat sterkere therapeutische effecten gerelateerd waren aan “(a) the degree of active therapist involvement with the patient; (b) an opportunity to experience meaningful objects and interpersonal activities; and (c) congenial settings that were reasonably free of artificiality, experimental or medical restrictions, and mechanically administered procedures” (1969). In de praktijk staat klinische therapie vaak ver van de theorie. Het zou kunnen zijn dat LSD, dat zelf ook een erg onvoorspelbaar middel is, in combinatie met de therapeutische dynamiek gewoonweg moeilijk is om te onderzoeken. “The administration of LSD is inextricably embedded in a larger psychosocial process”, concluderen Mogar en Aldrich, ”which should be optimized in accordance with particular treatment goals”.

Gezien de recente groei van aandacht voor dit onderzoeksveld, kan het nuttig zijn om deze oudere en nogal obscure studies te herevalueren. Onderzoekers van LA BioMed (Los Angeles Biomedical Research Institute) zijn momenteel een studie aan het opzetten waarin de effectiviteit van MDMA (3,4-methylenedioxy-N-methylamphetamine) bij de behandeling van sociale angst bij volwassenen met autisme zal worden onderzocht. Dit is de meest recente ontwikkeling in een groeiend programma van onderzoek naar de therapeutische eigenschappen van MDMA, gefinancierd door de non-profit Multidisciplinary Association for Psychedelic Studies (MAPS). “This new study will give us a chance”, zegt hoofd van het onderzoeksteam Charles Grob (2014), “to determine the actual effects of differing dosages of medication that we know for certain is pure MDMA on adults on the autism spectrum. If the results of this research warrant further investigation, data from this study will be used to design additional clinical trials”. Nu de beperkingen om de psychedelische ervaring en de therapeutische potentie van deze middelen te onderzoeken beginnen weg te vallen, en ook LSD weer opnieuw wordt onderzocht, kunnen de resultaten van deze oudere publicaties dienst doen voor het genereren van nieuwe hypothesen.

 
[1] Zie (Abramson, 1960; Bender, et al., 1962; Bender, et al., 1963; Fisher & Castile, 1963; Freedman, et al., 1962; Rolo, et al., 1965; Simmons, et al., 1966).
[2] Een gebruikelijke dosering LSD varieert van 100 tot 200 mcg, en een sterke dosering van 200 tot 600 mcg.
 
Referenties
Abramson, H.A. (Ed.) (1960). The Use of LSD in Psychotherapy. New York: Josiah Macy Foundation.
Bender, L., Faretra, G., & Cobrinik, L. (1963). LSD and UM-L treatment of hospitalized disturbed children. Recent Advances in Biological Psychiatry, 5, 84-92.
Bender, L., Goldschmidt, L., & Sankar, S.D.V. (1962). Treatment of autistic schizophrenic children with LSD-25 and UML-491. Recent Advances in Biological Psychiatry, 4, 170-177.
Cholden, L., Kurland, A., & Savage, C. (1955). Clinical reactions and tolerance to LSD in chronic schizophrenia. Journal of Nervous and Mental Disease, 122, 211-216.
Cohen, S., & Eisner, B. G. (1959). Use of lysergic acid diethylamide in a psychotherapeutic setting. AMA Archives of Neurology & Psychiatry, 81(5), 615-619.
Freedman, A.M., Ebin, E.V., & Wilson, E.A. (1962). Autistic schizophrenic children: An experiment in the use of d-lysergic acid diethylamide (LSD-25). Archives of General Psychiatry, 6, 203-213.
Gettys, T. (2014). MDMA Helps Reduce Social Anxiety for Autistic Adults, and Researchers Want to Find Out How. MAPS. Retrieved at: http://www.maps.org/media/view/mdma_helps_reduce_social_anxiety_for_autistic_adults_and_researchers_w/
Grof, S. (1980). LSD Psychotherapy. California: Hunter House Publishers.
Mogar, E. R., & Aldrich, W. R. (1969). The Use of Psychedelic Agents with Autistic Schizophrenic Children. Behavioral Neuropsychiatry, 1(8), 44-50.
Rolo, A., Krinsky. L.W., Abramson, H.A., & Goldfarb, L. (1965). Preliminary method for study of LSD with children. International Journal of Neuropsychiatry, 1, 552-555.
Sewell, R. A., Ranganathan, M., & D’Souza, D. C. (2009). Cannabinoids and psychosis. International Review of Psychiatry, 21(2), 152-162.
Simmons, J.Q., Leiken, SoJ., Lovaas, Q.I., Schaffer, B., & Perloff, B. (1966). Modification of autistic behavior with LSD-25. The American Journal of Psychiatry, 122, 1201-1211.

Autisme en LSD-25 – Het Bevrijden van de Meest Gevangen Geesten? Read More »

The effects of psilocybin and MDMA on between-network resting state functional connectivity in healthy volunteers

/ MDMA, Mushrooms / Psilocybin, Neuroscience, Papers, Psychology, Publications / / , , , ,

Abstract

Perturbing a system and observing the consequences is a classic scientific strategy for understanding a phenomenon. Psychedelic drugs perturb consciousness in a marked and novel way and thus are powerful tools for studying its mechanisms. In the present analysis, we measured changes in resting-state functional connectivity (RSFC) between a standard template of different independent components analysis (ICA)-derived resting state networks (RSNs) under the influence of two different psychoactive drugs, the stimulant/psychedelic hybrid, MDMA, and the classic psychedelic, psilocybin. Both were given in placebo-controlled designs and produced marked subjective effects, although reports of more profound changes in consciousness were given after psilocybin. Between-network RSFC was generally increased under psilocybin, implying that networks become less differentiated from each other in the psychedelic state. Decreased RSFC between visual and sensorimotor RSNs was also observed. MDMA had a notably less marked effect on between-network RSFC, implying that the extensive changes observed under psilocybin may be exclusive to classic psychedelic drugs and related to their especially profound effects on consciousness. The novel analytical approach applied here may be applied to other altered states of consciousness to improve our characterization of different conscious states and ultimately advance our understanding of the brain mechanisms underlying them.

Roseman, L., Leech, R., Feilding, A., Nutt, D. J., & Carhart-Harris, R. L. (2014). The effects of psilocybin and MDMA on between-network resting state functional connectivity in healthy volunteers. Frontiers in Human Neuroscience, 8, 1-11. http://dx.doi.org/10.3389/fnhum.2014.00204
Link to full text

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The effect of psilocin on memory acquisition, retrieval, and consolidation in the rat

/ Mushrooms / Psilocybin, Neuroscience, Papers, Publications / / , , ,

Abstract

The involvement of the serotonin system in the pathophysiology of schizophrenia has been elucidated by experiments with hallucinogens. Application of a hallucinogen to humans leads to changes in perception, cognition, emotions, and induction of psychotic-like symptoms that resemble symptoms of schizophrenia. In rodent studies, their acute administration affects sensorimotor gating, locomotor activity, social behavior, and cognition including working memory, the phenotypes are considered as an animal model of schizophrenia. The complexity and singularity of human cognition raises questions about the validity of animal models utilizing agonists of 5-HT2A receptors. The present study thus investigated the effect of psilocin on memory acquisition, reinforced retrieval, and memory consolidation in rats. Psilocin is a main metabolite of psilocybin acting as an agonist at 5-HT2A receptors with a contribution of 5-HT2C and 5-HT1A receptors. First, we tested the effect of psilocin on the acquisition of a Carousel maze, a spatial task requiring navigation using distal cues, attention, and cognitive coordination. Psilocin significantly impaired the acquisition of the Carousel maze at both doses (1 and 4 mg/kg). The higher dose of psilocin blocked the learning processes even in an additional session when the rats received only saline. Next, we examined the effect of psilocin on reinforced retrieval and consolidation in the Morris water maze (MWM). The dose of 4 mg/kg disrupted reinforced retrieval in the MWM. However, the application of a lower dose was without any significant effect. Finally, neither the low nor high dose of psilocin injected post-training caused a deficit in memory consolidation in the MWM. Taken together, the psilocin dose dependently impaired the acquisition of the Carousel maze and reinforced retrieval in MWM; however, it had no effect on memory consolidation.

Rambousek, L., Palenicek, T., Vales, K., & Stuchlik, A. (2014). The effect of psilocin on memory acquisition, retrieval, and consolidation in the rat. Frontiers in Behavioral Neuroscience, 8. https://dx.doi.org/10.3389/fnbeh.2014.00180
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Interaction of psychoactive tryptamines with biogenic amine transporters and serotonin receptor subtypes

/ DMT, LSD, MDMA, Mushrooms / Psilocybin, Papers, Publications / / , , , , ,

Abstract

Rationale
Synthetic hallucinogenic tryptamines, especially those originally described by Alexander Shulgin, continue to be abused in the USA. The range of subjective experiences produced by different tryptamines suggests that multiple neurochemical mechanisms are involved in their actions, in addition to the established role of agonist activity at serotonin 2A (5-HT2A) receptors.

Objectives
This study evaluated the interaction of a series of synthetic tryptamines with biogenic amine neurotransmitter transporters and with serotonin (5-HT) receptor subtypes implicated in psychedelic effects.

Methods
Neurotransmitter transporter activity was determined in rat brain synaptosomes. Receptor activity was determined using calcium mobilization and DiscoveRx PathHunter® assays in HEK293, Gα16-CHO, and CHOk1 cells transfected with human receptors.

Results
Twenty-one tryptamines were analyzed in transporter uptake and release assays, and 5-HT2A, serotonin 1A (5-HT1A), and 5-HT2A β-arrestin functional assays. Eight of the compounds were found to have 5-HT-releasing activity. Thirteen compounds were found to be 5-HT uptake inhibitors or were inactive. All tryptamines were 5-HT2A agonists with a range of potencies and efficacies, but only a few compounds were 5-HT1A agonists. Most tryptamines recruited β-arrestin through 5-HT2A activation.

Conclusions
All psychoactive tryptamines are 5-HT2A agonists, but 5-HT transporter (SERT) activity may contribute significantly to the pharmacology of certain compounds. The in vitro transporter data confirm structure-activity trends for releasers and uptake inhibitors whereby releasers tend to be structurally smaller compounds. Interestingly, two tertiary amines were found to be selective substrates at SERT, which dispels the notion that 5-HT-releasing activity is limited only to primary or secondary amines.

Blough, B. E., Landavazo, A., Decker, A. M., Partilla, J. S., Baumann, M. H., & Rothman, R. B. (2014). Interaction of psychoactive tryptamines with biogenic amine transporters and serotonin receptor subtypes. Psychopharmacology, 231(21), 4135-4144. http://dx.doi.org/10.1007/s00213-014-3557-7
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Survey: Ayahuasca Consumption in Europe

/ Ayahuasca, Publications /

survey_508

Researchers are calling for participants to complete an anonymous online questionnaire about their ayahuasca consumption. This information will be presented at the upcoming World Ayahuasca Conference in September 2014.

The researchers are looking for people living in Europe who have already used ayahuasca, including those who no longer partake. The aim of the questionnaire is to create a comprehensive profile of European ayahuasca users and better understand their motivation for drinking ayahuasca, as well as how it may have benefited them.

To take the survey, click here. The survey takes 15 minutes and is completely anonymous.

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Survey: Ayahuasca consumptie in Europa

/ Ayahuasca /

survey_508

Onderzoekers zijn op zoek naar deelnemers om een online vragenlijst in te vullen over hun ayahuasca consumptie. Deze informatie zal worden gepresenteerd tijdens de World Ayahuasca Conference in september 2014.

De onderzoekers zoeken mensen die in Europa wonen en ayahuasca hebben gebruikt, inclusief diegenen die dit niet meer doen. Het doel van de vragenlijst is het creëren van een uitgebreid profiel van Europese ayahuasca gebruikers en het beter begrijpen van hun motivatie om ayahuasca te drinken, alsmede de mogelijke voordelen die men hiervan heeft ondervonden.

Klik hier om de vragenlijst in te vullen. Dit duurt ongeveer 15 minuten en is volledig anoniem.

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Repeated lysergic acid diethylamide in an animal model of depression: Normalisation of learning behaviour and hippocampal serotonin 5-HT2 signalling

/ Depressive Disorders, LSD, Neuroscience, Papers, Psychology, Publications / / , , ,

Abstract

A re-balance of postsynaptic serotonin (5-HT) receptor signalling, with an increase in 5-HT1A and a decrease in 5-HT2A signalling, is a final common pathway multiple antidepressants share. Given that the 5-HT1A/2A agonist lysergic acid diethylamide (LSD), when repeatedly applied, selectively downregulates 5-HT2A, but not 5-HT1A receptors, one might expect LSD to similarly re-balance the postsynaptic 5-HT signalling. Challenging this idea, we use an animal model of depression specifically responding to repeated antidepressant treatment (olfactory bulbectomy), and test the antidepressant-like properties of repeated LSD treatment (0.13 mg/kg/d, 11 d). In line with former findings, we observe that bulbectomised rats show marked deficits in active avoidance learning. These deficits, similarly as we earlier noted with imipramine, are largely reversed by repeated LSD administration. Additionally, bulbectomised rats exhibit distinct anomalies of monoamine receptor signalling in hippocampus and/or frontal cortex; from these, only the hippocampal decrease in 5-HT2 related [35S]-GTP-gamma-S binding is normalised by LSD. Importantly, the sham-operated rats do not profit from LSD, and exhibit reduced hippocampal 5-HT2 signalling. As behavioural deficits after bulbectomy respond to agents classified as antidepressants only, we conclude that the effect of LSD in this model can be considered antidepressant-like, and discuss it in terms of a re-balance of hippocampal 5-HT2/5-HT1A signalling.

Buchborn, T., Schröder, H., Höllt, V., & Grecksch, G. (2014). Repeated lysergic acid diethylamide in an animal model of depression: Normalisation of learning behaviour and hippocampal serotonin 5-HT2 signalling. Journal of Psychopharmacology, 28(6), 545-552. https://dx.doi.org/10.1177/0269881114531666
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Psilocybin-Induced Decrease in Amygdala Reactivity Correlates with Enhanced Positive Mood in Healthy Volunteers

/ Depressive Disorders, Mushrooms / Psilocybin, Neuroscience, Papers, Psychology, Publications / / , , , , , ,

Abstract

Background
The amygdala is a key structure in serotonergic emotion-processing circuits. In healthy volunteers, acute administration of the serotonin 1A/2A/2C receptor agonist psilocybin reduces neural responses to negative stimuli and induces mood changes toward positive states. However, it is little-known whether psilocybin reduces amygdala reactivity to negative stimuli and whether any change in amygdala reactivity is related to mood change.

Methods
This study assessed the effects of acute administration of the hallucinogen psilocybin (.16 mg/kg) versus placebo on amygdala reactivity to negative stimuli in 25 healthy volunteers using blood oxygen level-dependent functional magnetic resonance imaging. Mood changes were assessed using the Positive and Negative Affect Schedule and the state portion of the State-Trait Anxiety Inventory. A double-blind, randomized, cross-over design was used with volunteers counterbalanced to receive psilocybin and placebo in two separate sessions at least 14 days apart.

Results
Amygdala reactivity to negative and neutral stimuli was lower after psilocybin administration than after placebo administration. The psilocybin-induced attenuation of right amygdala reactivity in response to negative stimuli was related to the psilocybin-induced increase in positive mood state.

Conclusions
These results demonstrate that acute treatment with psilocybin decreased amygdala reactivity during emotion processing and that this was associated with an increase of positive mood in healthy volunteers. These findings may be relevant to the normalization of amygdala hyperactivity and negative mood states in patients with major depression.

Kraehenmann, R., Preller, K. H., Scheidegger, M., Pokorny, T., Bosch, O. G., Seifritz, E., & Vollenwieder, F. X. (2014). Psilocybin-Induced Decrease in Amygdala Reactivity Correlates with Enhanced Positive Mood in Healthy Volunteers. Biological Psychiatry. http://dx.doi.org/10.1016/j.biopsych.2014.04.010
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Breath and Body: Scientific and Experiential Perspectives on Breathwork - September 23rd

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