OPEN Foundation

Scienitific Discipline

Psychedelics and cognitive liberty: Reimagining drug policy through the prism of human rights.

Abstract

This paper reimagines drug policy – specifically psychedelic drug policy – through the prism of human rights. Challenges to the incumbent prohibitionist paradigm that have been brought from this perspective to date – namely by calling for exemptions from criminalisation on therapeutic or religious grounds – are considered, before the assertion is made that there is a need to go beyond such reified constructs, calling for an end to psychedelic drug prohibitions on the basis of the more fundamental right to cognitive liberty. This central concept is explicated, asserted as being a crucial component of freedom of thought, as enshrined within Article 9 of the European Convention on Human Rights (ECHR). It is argued that the right to cognitive liberty is routinely breached by the existence of the system of drug prohibition in the United Kingdom (UK), as encoded within the Misuse of Drugs Act 1971 (MDA). On this basis, it is proposed that Article 9 could be wielded to challenge the prohibitive system in the courts. This legal argument is supported by a parallel and entwined argument grounded in the political philosophy of classical liberalism: namely, that the state should only deploy the criminal law where an individual’s actions demonstrably run a high risk of causing harm to others. Beyond the courts, it is recommended that this liberal, rights-based approach also inform psychedelic drug policy activism, moving past the current predominant focus on harm reduction, towards a prioritization of benefit maximization. How this might translate in to a different regulatory model for psychedelic drugs, a third way, distinct from the traditional criminal and medical systems of control, is tentatively considered. However, given the dominant political climate in the UK – with its move away from rights and towards a more authoritarian drug policy – the possibility that it is only through underground movements that cognitive liberty will be assured in the foreseeable future is contemplated.

Walsh, C. (2016). Psychedelics and Cognitive Liberty: Reimagining drug policy through the prism of human rights. International Journal of Drug Policy. dx.doi.org/10.1016/j.drugpo.2015.12.025

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A Double-Blind, Randomized, Placebo-Controlled, Dose-Frequency Study of Intravenous Ketamine in Patients With Treatment-Resistant Depression

Abstract

Objective:
Ketamine, an N-methyl-d-aspartate glutamate receptor antagonist, has demonstrated a rapid-onset antidepressant effect in patients with treatment-resistant depression. This study evaluated the efficacy of twice- and thrice-weekly intravenous administration of ketamine in sustaining initial antidepressant effects in patients with treatment-resistant depression.

Method:
In a multicenter, double-blind study, adults (ages 18–64 years) with treatment-resistant depression were randomized to receive either intravenous ketamine (0.5 mg/kg of body weight) or intravenous placebo, administered over 40 minutes, either two or three times weekly, for up to 4 weeks. Patients who discontinued double-blind treatment after at least 2 weeks for lack of efficacy could enter an optional 2-week open-label phase to receive ketamine with the same frequency as in the double-blind phase. The primary outcome measure was change from baseline to day 15 in total score on the Montgomery-Åsberg Depression Rating Scale (MADRS).

Results:
In total, 67 (45 women) of 68 randomized patients received treatment. In the twice-weekly dosing groups, the mean change in MADRS score at day 15 was −18.4 (SD=12.0) for ketamine and −5.7 (SD=10.2) for placebo; in the thrice-weekly groups, it was −17.7 (SD=7.3) for ketamine and −3.1 (SD=5.7) for placebo. Similar observations were noted for ketamine during the open-label phase (twice-weekly, −12.2 [SD=12.8] on day 4; thrice-weekly, −14.0 [SD=12.5] on day 5). Both regimens were generally well tolerated. Headache, anxiety, dissociation, nausea, and dizziness were the most common (≥20%) treatment-emergent adverse events. Dissociative symptoms occurred transiently and attenuated with repeated dosing.

Conclusions:
Twice-weekly and thrice-weekly administration of ketamine at 0.5 mg/kg similarly maintained antidepressant efficacy over 15 days.

Singh, J. B., Fedgchin, M., Daly, E. J., De Boer, P., Cooper, K., Lim, P., … & Kurian, B. (2016). A Double-Blind, Randomized, Placebo-Controlled, Dose-Frequency Study of Intravenous Ketamine in Patients With Treatment-Resistant Depression. American Journal of Psychiatry. http://dx.doi.org/10.1176/appi.ajp.2016.16010037
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Genotoxic evaluations in Wistar rats of the hallucinogenic plant extract ayahuasca

Abstract

Ayahuasca, a psychoactive infusion, is a sacrament used by indigenous and non-indigenous communities in Brazil and other countries. This beverage has vaunted healing properties; however, its use in a therapeutic context still lacks preclinical data to certify its safety and effectiveness. This study evaluated the genotoxic, mutagenic and cytotoxic potential of ayahuasca in Wistar rats after a single oral dose. Rats of both sexes were randomly distributed into five experimental groups (n=10): negative control that received filtered water, positive control that received doxorubicin and treated groups that received ayahuasca at 1, 5 and 15 times the usual dose taken in human religious rituals. The rats were euthanized 30 hours after dosage. Genotoxicity was evaluated by flow cytometry, comet assay and micronucleus test. Renal, hepatic and pancreatic functions were evaluated by serum analysis. Ayahuasca showed low genotoxicity, with an increased frequency of micronuclei only at the highest exposure level, and a non-observed-adverse-effect-level established at 5X the dose, or 1.5 mg/kg bw N,N-dimethyltryptamine a major component of the infusion. No cytotoxic effects were observed in the tested conditions. Furthermore, hepatic, renal and pancreatic functions remained without significant changes for all treated groups.

Pic-Taylor, A., Junior, W. M., Souza-Filho, J., Grisolia, C. K., & Caldas, E. D. (2016). Genotoxic evaluations in Wistar rats of the hallucinogenic plant extract ayahuasca. International Journal of Phytomedicine, 8(2). http://dx.doi.org/10.5138/ijpm.v8i2.1828
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As Molly Takes The Party Toll: MDMA Toxicity Presenting With Pulmonary Hemorrhage

Khalid, F., Kowsika, S., Ghobrial, I., & Rehman, S. (2016). As Molly Takes The Party Toll: MDMA Toxicity Presenting With Pulmonary Hemorrhage. In A46. LUNG DISEASE DUE TO OTC AND ILLICITS: CASE REPORTS (pp. A1616-A1616). American Thoracic Society.
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Influence of caffeine on 3,4-methylenedioxymethamphetamine-induced dopaminergic neuron degeneration and neuroinflammation is age-dependent

Abstract

Previous studies have demonstrated that caffeine administration to adult mice potentiates glial activation induced by 3,4-methylenedioxymethamphetamine (MDMA). As neuroinflammatory response seems to correlate with neurodegeneration, and the young brain is particularly vulnerable to neurotoxicity, we evaluated dopamine neuron degeneration and glial activation in the caudate-putamen (CPu) and substantia nigra pars compacta (SNc) of adolescent and adult mice. Mice were treated with MDMA (4 × 20 mg/kg), alone or with caffeine (10 mg/kg). Interleukin (IL)-1β, tumor necrosis factor (TNF)-α, neuronal nitric oxide synthase (nNOS) were evaluated in CPu, whereas tyrosine hydroxylase (TH), glial fibrillary acidic protein, and CD11b were evaluated in CPu and SNc by immunohistochemistry. MDMA decreased TH in SNc of both adolescent and adult mice, whereas TH-positive fibers in CPu were only decreased in adults. In CPu of adolescent mice, caffeine potentiated MDMA-induced glial fibrillary acidic protein without altering CD11b, whereas in SNc caffeine did not influence MDMA-induced glial activation. nNOS, IL-1β, and TNF-α were increased by MDMA in CPu of adults, whereas in adolescents, levels were only elevated after combined MDMA plus caffeine. Caffeine alone modified only nNOS. Results suggest that the use of MDMA in association with caffeine during adolescence may exacerbate the neurotoxicity and neuroinflammation elicited by MDMA. Previous studies have demonstrated that caffeine potentiated glial activation induced by 3,4-methylenedioxymethamphetamine (MDMA) in adult mice. In this study, caffeine was shown to potentiate MDMA-induced dopamine neuron degeneration in substantia nigra pars compacta, astrogliosis, and TNF-α levels in caudate-putamen of adolescent mice. Results suggest that combined use of MDMA plus caffeine during adolescence may worsen the neurotoxicity and neuroinflammation elicited by MDMA.

Frau, L., Costa, G., Porceddu, P. F., Khairnar, A., Castelli, M. P., Ennas, M. G., … & Morelli, M. (2016). Influence of caffeine on 3, 4‐methylenedioxymethamphetamine‐induced dopaminergic neuron degeneration and neuroinflammation is age‐dependent. Journal of neurochemistry, 136(1), 148-162. http://dx.doi.org/10.1111/jnc.13377

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Effects of Long-Term Ayahuasca Administration on Memory and Anxiety in Rats

Abstract

Ayahuasca is a hallucinogenic beverage that combines the action of the 5-HT2A/2C agonist N,N-dimethyltryptamine (DMT) from Psychotria viridis with the monoamine oxidase inhibitors (MAOIs) induced by beta-carbonyls from Banisteriopsis caapi. Previous investigations have highlighted the involvement of ayahuasca with the activation of brain regions known to be involved with episodic memory, contextual associations and emotional processing after ayahuasca ingestion. Moreover long term users show better performance in neuropsychological tests when tested in off-drug condition. This study evaluated the effects of long-term administration of ayahuasca on Morris water maze (MWM), fear conditioning and elevated plus maze (EPM) performance in rats. Behavior tests started 48h after the end of treatment. Freeze-dried ayahuasca doses of 120, 240 and 480 mg/kg were used, with water as the control. Long-term administration consisted of a daily oral dose for 30 days by gavage. The behavioral data indicated that long-term ayahuasca administration did not affect the performance of animals in MWM and EPM tasks. However the dose of 120 mg/kg increased the contextual conditioned fear response for both background and foreground fear conditioning. The tone conditioned response was not affected after long-term administration. In addition, the increase in the contextual fear response was maintained during the repeated sessions several weeks after training. Taken together, these data showed that long-term ayahuasca administration in rats can interfere with the contextual association of emotional events, which is in agreement with the fact that the beverage activates brain areas related to these processes.

Favaro, V. M., Yonamine, M., Soares, J. C. K., & Oliveira, M. G. M. (2015). Effects of Long-Term Ayahuasca Administration on Memory and Anxiety in Rats. PloS one, 10(12), e0145840. http://dx.doi.org/10.1371/journal.pone.0145840
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Neuroimaging in moderate MDMA use: A systematic review

Abstract

MDMA (“ecstasy”) is widely used as a recreational drug, although there has been some debate about its neurotoxic effects in humans. However, most studies have investigated subjects with heavy use patterns, and the effects of transient MDMA use are unclear. In this review, we therefore focus on subjects with moderate use patterns, in order to assess the evidence for harmful effects. We searched for studies applying neuroimaging techniques in man. Studies were included if they provided at least one group with an average of <50 lifetime episodes of ecstasy use or an average lifetime consumption of <100 ecstasy tablets. All studies published before July 2015 were included. Of the 250 studies identified in the database search, 19 were included.

There is no convincing evidence that moderate MDMA use is associated with structural or functional brain alterations in neuroimaging measures. The lack of significant results was associated with high methodological heterogeneity in terms of dosages and co-consumption of other drugs, low quality of studies and small sample sizes.

Mueller, F., Lenz, C., Steiner, M., Dolder, P. C., Walter, M., Lang, U. E., … & Borgwardt, S. (2016). Neuroimaging in moderate MDMA use: A systematic review. Neuroscience & Biobehavioral Reviews, 62, 21-34. http://dx.doi.org/10.1016/j.neubiorev.2015.12.010
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Therapy with Substance – Psycholytic psychotherapy in the twenty first century

Therapy with Substance: Psycholytic psychotherapy in the twenty first century by Dr Friederike Meckel Fischer, Muswell Hill Press, 2015.

In the field where psychedelics and psychotherapy overlap, there are two main schools: the school of psychedelic therapy, most popular in the United States, which aims to give people a complete mystical experience in a very limited number of high-dose sessions, in order to help them overcome problems or reach a certain state that will help transform the person’s life for the better. The therapist generally remains silent throughout the psychedelic sessions and lets happen whatever happens. Psycholytic therapy, on the other hand, generally involves lower doses and a higher number of sessions with a psychedelic substance, and aims to bring to the surface the causes of the problems in someone’s life. By going into these, and by talking about them during the experience, insight comes and the problems dissolve. This latter approach was mainly popular in Europe and is practiced to this day in unofficial settings.

Dr Meckel Fischer is a medical doctor who went on to study many alternative modalities of healing, most notably Holotropic Breathwork under Stanislav Grof and Psycholytic Therapy with the Swiss medical society for psycholytic therapy (SAEPT) under the guidance of Samuel Widmer. She practiced psycholytic therapy (which at that point had become illegal) for some time, until one of her clients reported her to the police. She was put on trial in Switzerland and convicted. This made it possible for her to describe her experience without fearing to be convicted again. The resulting book is both a fascinating personal account of the way she learned from psycholytic therapy herself and the insights she gathered through her many years of experience in treating people.

The first three chapters deal with Dr Meckel Fischer’s personal path to healing and understanding through different types of therapy after a deep crisis in one of her relationships. She started with regular cognitive therapy, but quickly moved on to depth-psychology, and then to transpersonal psychotherapy with the help of holotropic breathwork under the guidance of Grof. At some point Grof pointed her in the direction of therapy with substance and she dove into this path, externally claiming to do it strictly for professional reasons, while at the same time discovering that it really helped her on a personal level as well.

The author then goes on to give a brief description of what psychotherapy entails in her opinion. She emphasises that there has to be a motivation for change, but that this change can only be initiated by allowing the unconscious material to come to the surface. Effective therapy and lasting change can only happen if the root cause is addressed, which means that the unconscious and pre-conscious causes, that lie in the transpersonal and perinatal domains emphasised by Grof, are allowed to be integrated into consciousness. Meckel Fischer thinks traditional psychotherapy does not work on this level and is therefore rarely effective in treating deeper issues.

She subsequently describes the different substances used in psycholytic therapy, showing how all of them have both unique and general properties. She acknowledges that people both can and have to learn how to work with these substances, and that initial sessions can lack direction and purpose. With time and experience, the sessions become more focused and people learn how to access their unconscious more intentionally. Meckel Fischer is of the opinion that any guide in a psycholytic therapy session should use the substance themselves along with the patient, as this helps them to sense what is going on within the participant: “A mountain guide cannot lead a walker through territory that they have not explored personally”. Her arguments for this point of view are convincing, although they may be considered controversial from a western medical perspective.

Meckel Fischer identifies several tools that help the guide perform psycholytic therapy. These tools are somewhat specific to her, as they resonate with her professional experience and background, but they can be somewhat generalised. Among them are the therapist, the substance, family constellation work, live-body-work, the group and music. All these aspects influence the experience and some can be utilised to initiate or deepen a process within a participant. These tools are used throughout the session. The series of sessions moves a person through different stages: from beginner to graduate, from starting out on the path of self-discovery to knowing the way and being able to continue on their own.

She furthermore shows the different stations along the path to integrating deep unconscious material, from the core therapeutic issue, through psychosomatics, epigenetic and perinatal experiences towards spiritual experiences. Meckel Fischer gives many examples and shows how many of the stories of the people she guided fit the stages and stations she enumerates. It seems to be a universal process that is similar to the hero’s journey, popularised by Joseph Campbell.

The author ends with a discussion of the dangers and side effects of using psychoactive substances in psycholytic therapy. One of the most important dangers is of course the illegality, although she believes that under certain circumstances this can help participants to take responsibility for the process they are entering. She also briefly relates the process of psycholytic therapy to shamanism, healing and spirituality, but doesn’t really go into depths with regards to these ideas. In the concluding remarks, she hints at what lies beyond psycholytic therapy: something that isn’t therapy anymore, but that heals our worldview and makes us more integral with our environment and holistic in our outlook.

At times the impression arises that the author too readily claims that her personal experiences with certain substances are universal; this is especially tangible in the explanation of the effects of the different substances. In other cases, she acknowledges that her experience is hers alone, but the general tone of the former examples makes one think that she feels otherwise. Meckel Fischer mentions one way in which to conceptualise and practice psycholytic therapy, and does not envision the possibility that other ways are possible. However, the wisdom the book embodies generally sounds genuine. There are nuggets of wisdom that make one realise a deeper truth, like: “the intention expressed on the evening before the session signals the first stage of the process of integration”. Others run contrary to the idea that one session should be enough: “The ability to be ‘on a substance’, and learn to observe the inner self under its effects in a composed, centred and disciplined way, increases with practice”.

Overall, the book offers a great look into a very promising way of using psychedelics that can be integrated into our society quite easily, as it has built-in mechanisms for minimising risks and maximising positive outcomes, as well as the idea of medical/psychological supervision. It is a timely book, which can help to institutionalise the craft of psycholytic therapy into something that can be learned, practiced and taught to others through experience. Meckel Fischer also makes a great case for experienced practitioners to help newcomers. Moreover, disorders are viewed in a more integrative and holistic manner, showing that no-one is completely sane and no-one is completely mad, but that all can benefit from deep therapeutic work on the self. It is a book for everybody who’s interested in doing serious therapeutic work with psychedelics, either by themselves or, when legal constraints are removed, in the form of individual or group therapy.

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Antidepressant Effects of a Single Dose of Ayahuasca in Patients With Recurrent Depression: A SPECT Study

Abstract

Ayahuasca is an Amazonian botanical hallucinogenic brew which contains dimethyltryptamine, a 5-HT2A receptor agonist, and harmine, a monoamine-oxidase A inhibitor. Our group recently reported that ayahuasca administration was associated with fast-acting antidepressive effects in 6 depressive patients. The objective of the present work was to assess the antidepressive potentials of ayahuasca in a bigger sample and to investigate its effects on regional cerebral blood flow. In an open-label trial conducted in an inpatient psychiatric unit, 17 patients with recurrent depression received an oral dose of ayahuasca (2.2 mL/kg) and were evaluated with the Hamilton Rating Scale for Depression, the Montgomery-Asberg Depression Rating Scale, the Brief Psychiatric Rating Scale, the Young Mania Rating Scale, and the Clinician Administered Dissociative States Scale during acute ayahuasca effects and 1, 7, 14, and 21 days after drug intake. Blood perfusion was assessed eight hours after drug administration by means of single photon emission tomography. Ayahuasca administration was associated with increased psychoactivity (Clinician Administered Dissociative States Scale) and significant score decreases in depression-related scales (Hamilton Rating Scale for Depression, Montgomery-Asberg Depression Rating Scale, Brief Psychiatric Rating Scale) from 80 minutes to day 21. Increased blood perfusion in the left nucleus accumbens, right insula and left subgenual area, brain regions implicated in the regulation of mood and emotions, were observed after ayahuasca intake. Ayahuasca was well tolerated. Vomiting was the only adverse effect recorded, being reported by 47% of the volunteers. Our results suggest that ayahuasca may have fast-acting and sustained antidepressive properties. These results should be replicated in randomized, double-blind, placebo-controlled trials.
Sanches, R. F., de Lima, O. F., Dos Santos, R. G., Macedo, L. R., Maia-de-Oliveira, J. P., Wichert-Ana, L., … & Hallak, J. E. (2015). Antidepressant Effects of a Single Dose of Ayahuasca in Patients With Recurrent Depression: A SPECT Study. Journal of clinical psychopharmacology. http://dx.doi.org/10.1097/JCP.0000000000000436
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The epistemic innocence of psychedelic states

Abstract

One recent development in epistemology, the philosophical study of knowledge, is the notion of ‘epistemic innocence’ introduced by Bortolotti and colleagues. This concept expresses the idea that certain suboptimal cognitive processes may nonetheless have epistemic (knowledge-related) benefits. The idea that delusion or confabulation may have psychological benefits is familiar enough. What is novel and interesting is the idea that such conditions may also yield significant and otherwise unavailable epistemic benefits. I apply the notion of epistemic innocence to research on the transformative potential of psychedelic drugs. The popular epithet ‘hallucinogen’ exemplifies a view of these substances as fundamentally epistemically detrimental. I argue that the picture is more complicated and that some psychedelic states can be epistemically innocent. This conclusion is highly relevant to policy debates about psychedelic therapy. Moreover, analysing the case of psychedelics can shed further light on the concept of epistemic innocence itself.

Letheby, C. (2016). The epistemic innocence of psychedelic states. Consciousness and cognition, 39, 28-37. http://dx.doi.org/10.1016/j.concog.2015.11.012
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