Several lines of evidence suggest that classic (5HT2A agonist) hallucinogens have clinically relevant effects in alcohol and drug addiction. Although recent studies have investigated the effects of ...psilocybin in various populations, there have been no studies on the efficacy of psilocybin for alcohol dependence. We conducted a single-group proof-of-concept study to quantify acute effects of psilocybin in alcohol-dependent participants and to provide preliminary outcome and safety data. Ten volunteers with DSM-IV alcohol dependence received orally administered psilocybin in one or two supervised sessions in addition to Motivational Enhancement Therapy and therapy sessions devoted to preparation for and debriefing from the psilocybin sessions. Participants’ responses to psilocybin were qualitatively similar to those described in other populations. Abstinence did not increase significantly in the first 4 weeks of treatment (when participants had not yet received psilocybin), but increased significantly following psilocybin administration (p < 0.05). Gains were largely maintained at follow-up to 36 weeks. The intensity of effects in the first psilocybin session (at week 4) strongly predicted change in drinking during weeks 5–8 (r = 0.76 to r = 0.89) and also predicted decreases in craving and increases in abstinence self-efficacy during week 5. There were no significant treatment-related adverse events. These preliminary findings provide a strong rationale for controlled trials with larger samples to investigate efficacy and mechanisms.
TRIAL REGISTRATION: NCT02061293
Full text
Available for:
NUK, OILJ, SAZU, UKNU, UL, UM, UPUK
Abstract Background Hoasca (also called ayahuasca ) is a N , N -dimethyltryptamine (DMT) -containing psychedelic brew originally used for magico-religious purposes by Amerindian populations of the ...Amazon Basin. Recently, Brazilian syncretic churches have helped spread the ritual use of hoasca to Western societies. The aim of this study was to evaluate substance use, and neuropsychological and psychological functioning of regular hoasca users within a religious setting. Methods Assessment of socio-economic status, mood, personality traits, impulsiveness, drug use, quality of life, extrinsic and intrinsic religiosity, and neuropsychological function was performed on 30 volunteers from a U.S. branch of União do Vegetal (UDV), a Brazilian religion which uses hoasca ritually. We also assessed 27 non-hoasca-using control subjects matched by socio-demographic profile and church attendance. Mann–Whitney U, Chi-squared and Fisher's tests were used to analyze differences between groups. Spearman's association and simple logistic regression tests were used to analyze the impact of frequency of hoasca use on dependent variables. Results Relative to the control group, the UDV group demonstrated lower scores for depression ( p = 0.043, r = .27) and confusion ( p = 0.032, r = .29) as assessed by the Profile of Mood States (POMS); higher scores on the instrument Big Five Inventory (BFI) for the personality traits Agreeableness ( p = 0.028, r = .29) and Openness ( p = 0.037, r = .28); higher scores on the quality life domain Role limitations due to physical health as determined by the instrument Medical Outcomes Study Short Form-36 — SF-36 ( p = 0.035, r = .28); less recent use of alcohol ( p < 0.001, φ c = .57), greater past use of alcohol to intoxication ( p = 0.007, φ c = .36) and past use of cannabis ( p = 0.001, φ c = .45) as measured by the Addiction Severity Index (ASI), 5th edition; better score on a measure of memory vulnerability to proactive interference as measured by the California Verbal Learning Test — CVLT ( p = 0.040, r = .27). Lifetime use of hoasca was positively correlated with Role limitations due to physical health ( p = 0.032, rs = .39) and negatively associated with lifetime heavy alcohol use ( p = 0.034, OR = 0.979). Conclusions The findings indicate that religious use of hoasca does not adversely affect neuropsychological functioning and may have positive effects on substance abuse and mood.
Full text
Available for:
GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK, ZRSKP
N,N-dimethyltryptamine (DMT), a psychedelic compound identified endogenously in mammals, is biosynthesized by aromatic-L-amino acid decarboxylase (AADC) and indolethylamine-N-methyltransferase ...(INMT). Whether DMT is biosynthesized in the mammalian brain is unknown. We investigated brain expression of INMT transcript in rats and humans, co-expression of INMT and AADC mRNA in rat brain and periphery, and brain concentrations of DMT in rats. INMT transcripts were identified in the cerebral cortex, pineal gland, and choroid plexus of both rats and humans via in situ hybridization. Notably, INMT mRNA was colocalized with AADC transcript in rat brain tissues, in contrast to rat peripheral tissues where there existed little overlapping expression of INMT with AADC transcripts. Additionally, extracellular concentrations of DMT in the cerebral cortex of normal behaving rats, with or without the pineal gland, were similar to those of canonical monoamine neurotransmitters including serotonin. A significant increase of DMT levels in the rat visual cortex was observed following induction of experimental cardiac arrest, a finding independent of an intact pineal gland. These results show for the first time that the rat brain is capable of synthesizing and releasing DMT at concentrations comparable to known monoamine neurotransmitters and raise the possibility that this phenomenon may occur similarly in human brains.
Full text
Available for:
IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
The state of consciousness induced by N,N-dimethyltryptamine (DMT) is one of the most extraordinary of any naturally-occurring psychedelic substance. Users consistently report the complete ...replacement of normal subjective experience with a novel "alternate universe," often densely populated with a variety of strange objects and other highly complex visual content, including what appear to be sentient "beings." The phenomenology of the DMT state is of great interest to psychology and calls for rigorous academic enquiry. The extremely short duration of DMT effects-less than 20 min-militates against single dose administration as the ideal model for such enquiry. Using pharmacokinetic modeling and DMT blood sampling data, we demonstrate that the unique pharmacological characteristics of DMT, which also include a rapid onset and lack of acute tolerance to its subjective effects, make it amenable to administration by target-controlled intravenous infusion. This is a technology developed to maintain a stable brain concentration of anesthetic drugs during surgery. Simulations of our model demonstrate that this approach will allow research subjects to be induced into a stable and prolonged DMT experience, making it possible to carefully observe its psychological contents, and provide more extensive accounts for subsequent analyses. This model would also be valuable in performing functional neuroimaging, where subjects are required to remain under the influence of the drug for extended periods. Finally, target-controlled intravenous infusion of DMT may aid the development of unique psychotherapeutic applications of this psychedelic agent.
Health status of ayahuasca users Barbosa, Paulo Cesar Ribeiro; Mizumoto, Suely; Bogenschutz, Michael P. ...
Drug testing and analysis,
July-August 2012, Volume:
4, Issue:
7-8
Journal Article
We generated dose-response data for the endogenous and ultra-short-acting hallucinogen, N,N-dimethyltryptamine (DMT), in a cohort of experienced hallucinogen users, measuring multiple biological and ...psychological outcome measures. Subjective responses were quantified with a new rating scale, the HRS, which provided better resolution of dose effects than did the biological variables.
A tolerance study then was performed, in which volunteers received four closely spaced hallucinogenic doses of DMT. Subjective responses demonstrated no tolerance, while biological measures were inconsistently reduced over the course of the sessions. Thus, DMT remains unique among classic hallucinogens in its inability to induce tolerance to its psychological effects.
To assess the role of the 5-HT
A
site in mediating DMT's effects, a pindolol pre-treatment study was performed. Pindolol significantly increased psychological responses to DMT, suggesting a buffering effect of 5-HT
1
A
agonism on 5-HT
2-mediated psychedelic effects. These data are opposite to those described in lower animal models of hallucinogens' mechanisms of action.
Full text
Available for:
IJS, IMTLJ, KILJ, KISLJ, NUK, SBCE, SBJE, UL, UM, UPCLJ, UPUK
Reliability and convergent-discriminant validity of a Spanish version of the Hallucinogen Rating Scale (HRS) were assessed in two differentiated populations of hallucinogen users involving the ...retrospective assessment of drug effects. In Study 1 (immediate assessment), 75 European users of the South American hallucinogenic drink
ayahuasca answered the HRS 4 h after drug intake in their habitual setting. In Study 2 (delayed assessment), 56 adult polydrug users answered the HRS and a short form of the Addiction Research Center Inventory (ARCI) recalling the effects they experienced when they last took a hallucinogen, in order to test the convergent-discriminant validity of HRS with the scales of the standard questionnaire used in most studies involving psychoactive drugs. The HRS scales showed increases after both the immediate and delayed retrospective assessment of drug effects. Reliability data indicated that four of the six scales show an acceptable level of internal consistency. Significant but limited correlations were found between the Perception and Somaesthesia scales and the ARCI LSD scale, pointing out the questionnaire's construct validity. Thus, the HRS was sensitive to hallucinogenic drug effects other than those elicited by intravenous
N,
N-dimethyltryptamine (DMT), for which it was originally designed, and showed reasonable reliability and convergent validity. Results suggest its usefulness in the evaluation of subjective effects elicited by psychoactive drugs with hallucinogenic properties, and constitute a preliminary approach to the effects of
ayahuasca in European subjects.
Full text
Available for:
GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
Clinical research with hallucinogens has resumed after a generation's hiatus. To place these new studies in context, this article reviews the history of hallucinogens' use and abuse, discusses their ...pharmacological properties, and highlights previous human studies. Research with lysergic acid diethylamide and related hallucinogens with thousands of patients and control subjects was associated with acceptable safety when subjects were carefully screened, supervised, and followed up. Data were generated regarding hallucinogens' psychopharmacology, overlap with endogenous psychoses, and psychotherapeutic efficacy. Current American and European studies emphasize systematic psychopharmacology, in addition to psychotherapy protocols. Human hallucinogen research will help define unique mind-brain interfaces, and provide mechanistic hypotheses and treatment options for psychiatric disorders. It is critical that human hallucinogen research in the 1990s make use of state of the art methodologies, or consensually define when modifications are required. Training and supervisory issues also must be explicitly addressed.
A multinational, collaborative, biomedical investigation of the effects of hoasca (ayahuasca), a potent concoction of plant hallucinogens, was conducted in the Brazilian Amazon during the summer of ...1993. This report describes the psychological assessment of 15 long-term members of a syncretic church that utilizes hoasca as a legal, psychoactive sacrament as well as 15 matched controls with no prior history of hoasca ingestion. Measures administered to both groups included structured psychiatric diagnostic interviews, personality testing, and neuropsychological evaluation. Phenomenological assessment of the altered state experience as well as semistructured and open-ended life story interviews were conducted with the long-term use hoasca group, but not the hoasca-naive control group. Salient findings included the remission of psychopathology following the initiation of hoasca use along with no evidence of personality or cognitive deterioration. Overall assessment revealed high functional status. Implications of this unusual phenomenon and need for further investigation are discussed.
PDF
