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Therapeutic Application

Capturing the different health conditions that PAP may adress

Sustained subjective benefits of LSD for the treatment of end-of-life anxiety

LSD_clinical_trial_bottle_small

Earlier, we reported on the first study with LSD in human subjects in more than forty years, conducted in Switzerland by Peter Gasser and his team. A follow-up of this study [1], based on qualitative interviews with participants, indicates lasting positive outcomes.

The original double-blind, placebo-controlled study was carried out on a sample of twelve subjects, nine of which went on to complete the full course of the study, including the 12-month follow-up. The participants, all terminally ill, underwent 6-8 non-drug psychotherapeutic sessions and two LSD experiences conducted by a co-therapist dyad. The four subjects who initially received the active placebo of 20µg of LSD were offered the possibility to take two full experimental 200µg-doses of LSD at the end of the actual study, an opportunity that was taken by three of them, who were subsequently included in the qualitative interviews.

All subjects had previously displayed significant anxiety and/or depression related to their life-threatening health situation. All of them reported considerable long-term benefits, among which are reduced anxiety, less fear of death, and an improved quality of life. Interestingly, most of them also reported positive changes in personality, which could be a subjective confirmation of the quantitative measures of trait anxiety (as opposed to state anxiety) that were reported. These trait measures dropped significantly after the LSD sessions, and remained low at the 12-month follow-up [2].

In subjective reports of the LSD sessions, participants described facilitated access to emotions and catharsis. Facing a short life prognosis, they reported that LSD intensified and allowed expression of associated emotions. The interviews suggest the patients benefited from this intensified emotional experience. LSD also enabled them to view themselves and their difficult situation in a new, broader perspective. “Dying is as usual or unusual as life itself,” said one patient. “I simply have to familiarize myself with the idea and the process.” The patients also reported drastic shifts in emotions during or between the two sessions, usually beginning with ‘negative’ feelings related to their life situation, such as anxiety, depression and hopelessness. This reportedly negative emotional state transformed into a positive one, felt with an intensity never experienced before and lasting for at least one year after the sessions. Although they were facing ongoing severe somatic diseases, none of the participants reported any adverse effects from the psychedelic sessions.

Another interesting aspect is the approach that was chosen. Two different approaches emerged from the early research with LSD between the 1950s and the 1970s. In psycholytic therapy, used mainly in Europe, patients underwent a high number of psychoanalytically oriented psychotherapeutic sessions with low to medium dosages of LSD (50-100 µg). The psychedelic approach, on the other hand, aimed to elicit mystical or peak experiences in patients by administering them high doses (200-500 µg) in a limited number of sessions. This latter method was more frequently used in the United States, and up to now, it is the only approach that was used in the treatment of end-of-life anxiety.

In the Swiss study, the approach was very much akin to the psychedelic method, however staying on the low side of the dosage range. The setting was also somewhat looser than in the traditional psychedelic approach, where the subject kept on eyeshades most of the time while listening to music through headphones. Most of the resulting experiences could be described as ‘peak experiences’, but do not match the criteria for full mystical experiences. These two types of experiences can be quite similar. Ego boundaries are loosened in peak experiences, but don’t dissolve completely as in mystical experiences. Intellectual functions also stay intact to a greater degree, which allows for a higher degree of interaction between subject and guiding therapists than in the traditional psychedelic approach. These peak experiences seem to be the main psychological mechanism of action involved, much more so than the cognitive and psychodynamic experiences that are also frequent as a result of LSD administration.

The Swiss study’s approach certainly has advantages, one of which being that it seems to normalize the results for all participants. In past studies with psychedelics for end-of-life anxiety, conducted during the first era of psychedelic research, the typical outcome would show a dramatic improvement in about one-third of the subjects, a moderate improvement in another third, and no significant changes in the remaining third [3]. In the present study, remarkably, every single patient experienced significant improvement, although none reported ‘dramatic’ effects. This result certainly warrants further study, especially in light of the development of different therapeutic approaches to be used in psychedelic therapy.


 
[1] Gasser, P., Kirchner, K., & Passie, T. (2014).
[2] Gasser, P., Holstein, D., Michel, Y., Doblin, R., Yazar-Klosinski, B., Passie, T., & Brenneisen, R. (2014).
[3] Kurland, A.A. (1985).
 
References
Gasser, P., Kirchner, K. & Passie, T. (2014). LSD-assisted psychotherapy for anxiety associated with a life-threatening disease: A qualitative study of acute and sustained subjective effects. Journal of Psychopharmacology, 29(1), 57-68. [Abstract]
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(7), 513–520. [Abstract]
Kurland, A.A. (1985). LSD in the supportive care of the terminally ill cancer patient. Journal of Psychoactive Drugs, 17(4), 279–290. [Link to full text]

Classic psychedelic use is associated with reduced psychological distress and suicidality in the United States adult population

Abstract

Mental health problems are endemic across the globe, and suicide, a strong corollary of poor mental health, is a leading cause of death. Classic psychedelic use may occasion lasting improvements in mental health, but the effects of classic psychedelic use on suicidality are unknown. We evaluated the relationships of classic psychedelic use with psychological distress and suicidality among over 190,000 USA adult respondents pooled from the last five available years of the National Survey on Drug Use and Health (2008–2012) while controlling for a range of covariates. Lifetime classic psychedelic use was associated with a significantly reduced odds of past month psychological distress (weighted odds ratio (OR)=0.81 (0.72–0.91)), past year suicidal thinking (weighted OR=0.86 (0.78–0.94)), past year suicidal planning (weighted OR=0.71 (0.54–0.94)), and past year suicide attempt (weighted OR=0.64 (0.46–0.89)), whereas lifetime illicit use of other drugs was largely associated with an increased likelihood of these outcomes. These findings indicate that classic psychedelics may hold promise in the prevention of suicide, supporting the view that classic psychedelics’ most highly restricted legal status should be reconsidered to facilitate scientific study, and suggesting that more extensive clinical research with classic psychedelics is warranted.

Hendricks, P. S., Thorne, C. B., Clark, C. B., Coombs, D. W., & Johnson, M. W. (2015). Classic psychedelic use is associated with reduced psychological distress and suicidality in the United States adult population. Journal of Psychopharmacology. https://dx.doi.org/10.1177/0269881114565653

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Psilocybin-assisted treatment for alcohol dependence: A proof-of-concept study

Abstract

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.

Bogenschutz, M. P., Forcehimes, A. A, Pommy, J. A., Wilcox, C. E., Barbosa, P. C. R., & Strassman, R. J. (2015). Psilocybin-assisted treatment for alcohol dependence: A proof-of-concept study. Journal of Psychopharmacology. https://dx.doi.org/10.1177/0269881114565144

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Making a medicine out of MDMA

Abstract

From its first use 3,4,-methylenedioxymethamphetamine (MDMA) has been recognised as a drug with therapeutic potential. Research on its clinical utility stopped when it entered the recreational drug scene but has slowly resurrected in the past decade. Currently there is enough evidence for MDMA to be removed from its Schedule 1 status of ‘no medical use’ and moved into Schedule 2 (alongside other misused but useful medicines such as heroin and amphetamine). Such a regulatory move would liberate its use as a medicine for patients experiencing severe mental illnesses such as treatment-resistant post-traumatic stress disorder.

Sessa, B., & Nutt, D. (2015). Making a medicine out of MDMA. The British Journal of Psychiatry, 206, 4-6. https://dx.doi.org/10.1192/bjp.bp.114.152751

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Can psychedelic compounds play a part in drug dependence therapy?

Abstract

After a 40-year hiatus there is now a revisiting of psychedelic drug therapy throughout psychiatry, with studies examining the drugs psilocybin, ketamine, ibogaine and ayahuasca in the treatment of drug dependence. Limitations to these therapies are both clinical and legal, but the possibility of improving outcomes for patients with substance dependency imposes an obligation to research this area.

Sessa, B., & Johnson, M. W. (2015). Can psychedelic compounds play a part in drug dependence therapy? The British Journal of Psychiatry, 206, 1-3. https://dx.doi.org/10.1192/bjp.bp.114.148031

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Psychedelic-facilitated smoking cessation: An online survey

Abstract

Aims:
Pilot laboratory results suggest psilocybin may be an efficacious adjunct to smoking cessation treatment. However, no study has examined smoking cessation after psychedelic use in naturalistic settings.
Methods:
We are conducting an online survey collecting demographics, smoking history, and other data from people who self-report quitting/reducing smoking after taking a psychedelic.
Results:
Among current completers (N=164), LSD (49%) and psilocybin (32%) were the drugs most commonly associated with quitting/reducing, with a mode of 2-5 lifetime uses each. Participants reported smoking a mean of 12 cigs/day for a mean of 8 yrs before the experience. 62(38%) reported total and continuing abstinence after their experience, with 29 of the 62 (47%) reporting >1yr abstinence, and 7 (11%) reporting >10 yrs abstinence. Another 67 of the 164 (41%) reported persisting smoking reduction, from a mode of 10-20 cigs/day before, to a mode of <1 cig/month after the experience. The remaining 35 (21%) reported temporary reduction, with 6 of the 35 (17%) reporting >1 yr reduction. Although the majority of withdrawal symptoms were rated as equal in severity to previous quit attempts, depression, irritability, anxiety, and craving were rated as “much less severe.” 141 of the 164 (86%) reported no premeditated intention to quit/reduce smoking, and 159 (97%) described their experience as highly meaningful, with
97 (59%) considering it among the 10 most meaningful experiences of their lives. Participants cited changed life priorities/values (26%), strengthened belief in their ability to quit (26%), and changed future orientation (17%) as the most important effects leading to quitting/reducing. Other changes reported after psychedelic use included reduced alcohol (38%) and other drug use (23%).
Conclusions:
Psychedelics may prompt temporary or prolonged smoking cessation, suggesting that careful administration in a treatment context may enhance motivation in changing addictive behaviors. Psychological and neurobiological mechanisms underlying such behavioral changes require further investigation.

Garcia-Romeu, A. P., Griffiths, R. R., & Johnson, M. W. (2015). Psychedelic-facilitated smoking cessation: An online survey. Drug and Alcohol Dependence, (146), e120. http://dx.doi.org/10.1016/j.drugalcdep.2014.09.245
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Rapid-onset antidepressant action of ketamine: potential revolution in understanding and future pharmacologic treatment of depression

Summary

What is known and objective

The current pharmacotherapeutic treatment of major depressive disorder (MDD) generally takes weeks to be effective. As the molecular action of these drugs is immediate, the mechanistic basis for this lag is unclear. A drug that has a more rapid onset of action would be a major therapeutic advance and also be a useful comparator to provide valuable mechanistic insight into the disorder and its treatment.

Comment

Recent evidence suggests that ketamine produces rapid-onset antidepressant action. Important questions are as follows: is it specific or coincidental to other effects; is there a dose–response relationship; and is the mechanism related to that of current antidepressants. NMDA receptor antagonism is unlikely the explanation for ketamine’s antidepressant action.

What is new and conclusion

It is not an exaggeration to state that the new findings, if validated, might produce a revolution in understanding and treating depressive disorders.

Drewniany, E., Han, J., Hancock, C., Jones, R. L., Lim, J., Nemat Gorgani, N., … & Raffa, R. B. (2014). Rapid‐onset antidepressant action of ketamine: potential revolution in understanding and future pharmacologic treatment of depression. Journal of Clinical Pharmacy and Therapeutics. https://dx.doi.org/10.1111/jcpt.12238
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Synthesis and κ-opioid receptor activity of furan-substituted salvinorin A analogues

Abstract

The neoclerodane diterpene salvinorin A, found in the leaves of Salvia divinorum, is a potent κ-opioid receptor agonist, making it an attractive scaffold for development into a treatment for substance abuse. Although several successful semisynthetic studies have been performed to elucidate structure-activity relationships, the lack of analogues with substitutions to the furan ring of salvinorin A has prevented a thorough understanding of its role in binding to the κ-opioid receptor. Herein we report the synthesis of several salvinorin A derivatives with modified furan rings. Evaluation of these compounds in a functional assay indicated that sterically less demanding substitutions are preferred, suggesting the furan ring is bound in a congested portion of the binding pocket. The most potent of the analogues successfully reduced drug-seeking behavior in an animal model of drug-relapse without producing the sedation observed with other κ-opioid agonists.

Riley, A. P., Groer, C. E., Young, D., Ewald, A. W., Kivell, B. M., & Prisinzano, T. E. (2014). Synthesis and Kappa Opioid Receptor Activity of Furan-Substituted Salvinorin A Analogues. Journal of medicinal chemistry. https://dx.doi.org/10.1021/jm501521d
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Neurocognitive Effects of Ketamine and Association with Antidepressant Response in Individuals with Treatment-Resistant Depression: A Randomized Controlled Trial

Abstract

The glutamate N-methyl-D-aspartate (NMDA) receptor antagonist ketamine displays rapid antidepressant effects in patients with treatment-resistant depression (TRD); however, the potential for adverse neurocognitive effects in this population has not received adequate study. The current study was designed to investigate the delayed neurocognitive impact of ketamine in TRD and examine baseline antidepressant response predictors in the context of a randomized controlled trial. In the current study, 62 patients (mean age=46.2±12.2) with TRD free of concomitant antidepressant medication underwent neurocognitive assessments using components of the MATRICS Consensus Cognitive Battery (MCCB) before and after a single intravenous infusion of ketamine (0.5mg/kg) or midazolam (0.045mg/kg). Participants were randomized to ketamine or midazolam in a 2:1 fashion under double-blind conditions and underwent depression symptom assessments at 24, 48, 72h, and 7 days post treatment using the Montgomery–Asberg Depression Rating Scale (MADRS). Post-treatment neurocognitive assessment was conducted once at 7 days. Neurocognitive performance improved following the treatment regardless of treatment condition. There was no differential effect of treatment on neurocognitive performance and no association with antidepressant response. Slower processing speed at baseline uniquely predicted greater improvement in depression at 24h following ketamine (t=2.3, p=0.027), while controlling for age, depression severity, and performance on other neurocognitive domains. In the current study, we found that ketamine was devoid of adverse neurocognitive effects at 7 days post treatment and that slower baseline processing speed was associated with greater antidepressant response. Future studies are required to further define the neurocognitive profile of ketamine in clinical samples and to identify clinically useful response moderators.

Murrough, J. W., Burdick, K. E., Levitch, C. F., Perez, A. M., Brallier, J. W., Chang, L. C., … & Iosifescu, D. V. (2014). Neurocognitive Effects of Ketamine and Association with Antidepressant Response in Individuals with Treatment-Resistant Depression: A Randomized Controlled Trial. Neuropsychopharmacology. https://dx.doi.org/10.1038/npp.2014.298

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Medical Drug or Shamanic Power Plant: The Uses of Kambô in Brazil

Abstract

The secretion from the frog Phyllomedusa bicolor, known in Portuguese as kambô, has traditionally been used as a stimulant and an invigorating agent for hunting by indigenous groups such as the Katukina, Yawanawa, and the Kaxinawa in the southeast Amazon. Since the mid 90s, its use has expanded to large cities in Brazil and, since the late 2000s, abroad to Europe and the US. The urban diffusion of the use of kambô has taken place via healing clinics offering alternative therapies, by way of members of the Brazilian ayahuasca religions, and through travel, mainly by Amazonian rubber tappers, the Katukina, and the Kawinawa Indians. In this article, we present an ethnography of the expansion and reinvention of the use of kambô. We describe the individuals who apply the substance, who are a diverse group, including indigenous healers, ex-rubber tappers, holistic therapists, and doctors. We argue that the frog secretion has a double appeal among this new urban clientele: as a “remedy of science,” in which its biochemical properties are stressed; and as a “remedy of spirit,” in which its “indigenous origin” is more valued, as if kambô was a kind of shamanic power plant analogous to peyote and ayahuasca.

Labate, B. C., & Lima, E. C. D. (2014). Medical Drug or Shamanic Power Plant: The Uses of Kambô in Brazil. Ponto Urbe. Revista do núcleo de antropologia urbana da USP, (15).
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