OPEN Foundation

LSD

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

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.

Interaction of psychoactive tryptamines with biogenic amine transporters and serotonin receptor subtypes

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
Link to full text

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

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
Link to full text

Why Psychiatry Needs Psychedelics and Psychedelics Need Psychiatry

Abstract

Without researching psychedelic drugs for medical therapy, psychiatry is turning its back on a group of compounds that could have great potential. Without the validation of the medical profession, the psychedelic drugs, and those who take them off-license, remain archaic sentiments of the past, with the users maligned as recreational drug abusers and subject to continued negative opinion. These two disparate groups—psychiatrists and recreational psychedelic drug users—are united by their shared recognition of the healing potential of these compounds. A resolution of this conflict is essential for the future of psychiatric medicine and psychedelic culture alike. Progression will come from professionals working in the field adapting to fit a conservative paradigm. In this way, they can provide the public with important treatments and also raise the profile of expanded consciousness in mainstream society.

Sessa, B. (2014). Why Psychiatry Needs Psychedelics and Psychedelics Need Psychiatry. Journal of Psychoactive Drugs, 46(1), 57–62. http://dx.doi.org/10.1080/02791072.2014.877322
Link to full text

History and Future of the Multidisciplinary Association for Psychedelic Studies (MAPS)

Abstract

This article describes the teenage vision of the founder of the Multidisciplinary Association for Psychedelic Studies (MAPS) that humanity’s future would be aided by the therapeutic and spiritual potential of psychedelic substances. The article traces the trajectory of MAPS from inception in 1986 to its present, noting future goals with respect to research, outreach, and harm reduction. MAPS was created as a non-profit psychedelic pharmaceutical company in response to the 1985 scheduling of 3,4-methylenedioxymethamphetamine (MDMA). Overcoming many hurdles, MAPS developed the first double-blind, placebo-controlled trial of MDMA-assisted psychotherapy for posttraumatic stress disorder (PTSD) and plans for FDA prescription approval in 2021. MAPS’ program of research expanded to include a trial of lysergic acid diethylamide (LSD)-assisted psychotherapy for anxiety when facing life-threatening illness, observational studies of ibogaine in the treatment of addiction, and studies of MDMA for social anxiety in people with autism spectrum disorders. MAPS meets the challenges of drug development through a clinical research team led by a former Novartis drug development professional experienced in the conduct, monitoring, and analysis of clinical trials. MAPS’ harm-reduction efforts are intended to avoid backlash and build a post-prohibition world by assisting non-medical users to transform difficult psychedelic experiences into opportunities for growth.

Emerson, A., Ponté, L., Jerome, L., & Doblin, R. (2014). History and Future of the Multidisciplinary Association for Psychedelic Studies (MAPS). Journal of Psychoactive Drugs, 46(1), 27–36. http://dx.doi.org/10.1080/02791072.2014.877321
Link to full text

Self-Experimentations with Psychedelics Among Mental Health Professionals: LSD in the Former Czechoslovakia

Abstract

This article enquires into auto-experiments with psychedelics. It is focused on the experiences and current attitudes of mental health professionals who experimented with LSD in the era of legal research of this substance in the former Czechoslovakia. The objective of the follow-up study presented was to assess respondents’ long-term views on their LSD experience(s). A secondary objective was to capture the attitude of the respondents toward the use of psychedelics within the mental health field. A total of 22 individuals participated in structured interviews. None of the respondents reported any long-term negative effect and all of them except two recorded enrichment in the sphere of self-awareness and/or understanding to those with mental disorder(s). Although there were controversies with regard to the ability of preventing possible negative consequences, respondents were supportive towards self-experiments with LSD in mental health sciences. This article is the first systematic examination of the self-experimentation with psychedelics that took place east of the Iron Curtain.

Winkler, P., & Csémy, L. (2014). Self-Experimentations with Psychedelics Among Mental Health Professionals: LSD in the Former Czechoslovakia. Journal of Psychoactive Drugs, 46(1), 11–19. http://dx.doi.org/10.1080/02791072.2013.873158
Link to full text

From Hofmann to the Haight Ashbury, and into the Future: The Past and Potential of Lysergic Acid Diethlyamide

Abstract

Since the discovery of its psychedelic properties in 1943, lysergic acid diethylamide (LSD) has been explored by psychiatric/therapeutic researchers, military/intelligence agencies, and a significant portion of the general population. Promising early research was halted by LSD’s placement as a Schedule I drug in the early 1970s. The U.S. Army and CIA dropped their research after finding it unreliable for their purposes. NSDUH estimates that more than 22 million (9.1% of the population) have used LSD at least once in their lives. Recently, researchers have been investigating the therapeutic use of LSD and other psychedelics for end-of-life anxiety, post-traumatic stress disorder (PTSD), cancer, and addiction treatment. Adverse psychedelic reactions can be managed using talkdown techniques developed and in use since the 1960s.

Smith, D. E., Raswyck, G. E., & Leigh Dickerson Davidson, L. (2014). From Hofmann to the Haight Ashbury, and into the Future: The Past and Potential of Lysergic Acid Diethlyamide. Journal of Psychoactive Drugs, 46(1), 3–10. http://dx.doi.org/10.1080/02791072.2014.873684
Link to full text

Hofmann’s Wish Came True

After 40 years without research, the recent appearance of a pilot study with Lysergic Acid Diethylamide (LSD) in humans, might be interpreted as a positive reinforcement for future attempts to study the role of psychedelics as therapeutic agents. The study of Gasser et al. (2014) was aimed at assaying the possible benefits from the use of LSD as an additive to psychotherapy in the treatment of anxiety associated with life-threatening diseases.

The participants in the double blind, randomized, active placebo-controlled study were recruited from a population of patients diagnosed with a life-threatening disease. The participants were randomized across two-groups and received two therapeutic sessions with LSD (mild-dose placebo-control group; moderate-dose experimental group) in addition to psychotherapy. The patients that were initially assigned to the placebo-control group, were offered the opportunity to participate in a second series of moderate-dose LSD-assisted therapies (open-label crossover group). The most important result from the study was that with each cumulative LSD session, anxiety seemed to reduce in the group that received a moderate dose, but not in the group that received a mild dose. In the latter group, this pattern of reduced anxiety was repeated with the second series of sessions in which the moderate dose was offered to the patients. The benefits of the LSD-assisted sessions seemed to sustain over time. Though methodological adjustments are preferred to improve matters of experimental reliability and validity (as the authors note a larger sample size, a less discriminative placebo, better treatment of secondary disease symptoms to avoid missing data), the reactions of the patients themselves suggest successful clinical guidance during the process of coping with death. Majority reported that they would have preferred more than two LSD sessions and a longer treatment period.

Not only did the study yield promising results about the controversial use of a Schedule 1 listed drug (21 U.S.C. § 812) in a therapeutic setting, the publication also received extensive international media attention (Carey, 2014; Healey, 2014; Connor, 2014) suggesting a regained public interest favoring psychedelic research. While directly after discovery the psychoactive effects of LSD were considered to be of considerable value for experimental research and psychiatric practice (Passie, Halpern, Stichtenoth, Emrich, & Hintzen, 2008), it’s reputation of the past 40 years was mainly that of a dangerous drug (SAMHSHA, 2008). In addition to a recent clinical study done with psilocybin (Grob et al., 2011) , the current study contributes to a refreshed wave that acknowledges the usefulness of psychedelics as an investigational tool for psychiatric research. With the resumption of research into LSD’s therapeutic potential, the researchers hope to have “fulfilled the longtime wish” of the founding father of LSD, Albert Hofmann, as to whom the article is dedicated.


 
References
Carey, B. (2014, March 4). LSD, Reconsidered for Therapy. The New York Times. Retrieved from http://www.nytimes.com
Connor, S. (2014, March 6). Can LSD ease our fear of death? First scientific study in 40 years shows positive results. The independent. Retrieved from http://www.independent.co.uk
Gasser, P., Holstein, D., Michel, Y., Doblin, R., Yazar-Klosinski, B., Passie, T., Brenneisen, R. (in press). Safety and Efficacy of Lysergic Acid Diethylamide-Assisted Psychotherapy for Anxiety Associated With Life-threatening Diseases. The Journal of Nervous and Mental Disease
Grob, C. S., Danforth, A. L., Chopra, G. S., Hagerty, M., McKay, C. R., Halberstadt, A. L., & Greer, G. R. (2011). Pilot study of psilocybin treatment for anxiety in patients with advanced-stage cancer. Archives of General Psychiatry, 68, 71–78. doi:10.1001/archgenpsychiatry.2010.116
Healy, M. (2014, March 5). First trial of LSD as medicine in 40 years shows promise. The Los Angeles Times. Retrieved from http://www.latimes.com
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, 295–314. doi:10.1111/j.1755-5949.2008.00059.x
SAMHSA. Available at http://www.oas.samhsa.gov/ecstasy.htm, 2006. Accessed on 08 March 2014.
U.S. Food and Drug Administration. (2009, June 6). Controlled Substance Act. Retrieved from http://www.fda.gov/regulatoryinformation/legislation/ucm148726.htm

Safety and Efficacy of Lysergic Acid Diethylamide-Assisted Psychotherapy for Anxiety Associated With Life-threatening Diseases

Abstract

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 mcg of LSD (n=8) or 20 mcg of LSD with an open-label crossover to 200 mcg 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.

Gasser, P., Holstein, D., Michel, Y., Doblin, R., Yazar-Klosinski, B., Passie, T., & Brenneisen, R. (2014). Safety and Efficacy of Lysergic Acid Diethylamide-Assisted Psychotherapy for Anxiety Associated With Life-threatening Diseases. The Journal of Nervous and Mental Disease, 202, 1-8. http://dx.doi.org/10.1097/NMD.0000000000000113
Link to full text

The entropic brain: a theory of conscious states informed by neuroimaging research with psychedelic drugs

Abstract

Entropy is a dimensionless quantity that is used for measuring uncertainty about the state of a system but it can also imply physical qualities, where high entropy is synonymous with high disorder. Entropy is applied here in the context of states of consciousness and their associated neurodynamics, with a particular focus on the psychedelic state. The psychedelic state is considered an exemplar of a primitive or primary state of consciousness that preceded the development of modern, adult, human, normal waking consciousness. Based on neuroimaging data with psilocybin, a classic psychedelic drug, it is argued that the defining feature of “primary states” is elevated entropy in certain aspects of brain function, such as the repertoire of functional connectivity motifs that form and fragment across time. Indeed, since there is a greater repertoire of connectivity motifs in the psychedelic state than in normal waking consciousness, this implies that primary states may exhibit “criticality,” i.e., the property of being poised at a “critical” point in a transition zone between order and disorder where certain phenomena such as power-law scaling appear. Moreover, if primary states are critical, then this suggests that entropy is suppressed in normal waking consciousness, meaning that the brain operates just below criticality. It is argued that this entropy suppression furnishes normal waking consciousness with a constrained quality and associated metacognitive functions, including reality-testing and self-awareness. It is also proposed that entry into primary states depends on a collapse of the normally highly organized activity within the default-mode network (DMN) and a decoupling between the DMN and the medial temporal lobes (which are normally significantly coupled). These hypotheses can be tested by examining brain activity and associated cognition in other candidate primary states such as rapid eye movement (REM) sleep and early psychosis and comparing these with non-primary states such as normal waking consciousness and the anaesthetized state.

Carhart-Harris, R. L., Leech, R., Hellyer, P. J., Shanahan, M., Feilding, A., Tagliazucchi, E., Chialvo, D. R., & Nutt, D. (2014). The entropic brain: a theory of conscious states informed by neuroimaging research with psychedelic drugs. Frontiers in Human Neuroscience, 8, 1-22. http://dx.doi.org/10.3389/fnhum.2014.00020
Link to full text

interested in becoming a trained psychedelic-assisted therapist?

Management of Psychedelic-Related Complications - Online Event - Nov 20th