OPEN Foundation

Menu
Search
Close this search box.

MDMA

Chronic MDMA induces neurochemical changes in the hippocampus of adolescent and young adult rats: Down-regulation of apoptotic markers

June 9, 2015 / MDMA, Neuroscience, Papers, Publications / By / ,

Abstract

While hippocampus is a brain region particularly susceptible to the effects of MDMA, the cellular and molecular changes induced by MDMA are still to be fully elucidated, being the dosage regimen, the species and the developmental stage under study great variables. This study compared the effects of one and four days of MDMA administration following a binge paradigm (3×5 mg/kg, i.p., every 2 h) on inducing hippocampal neurochemical changes in adolescent (PND 37) and young adult (PND 58) rats. The results showed that chronic MDMA caused hippocampal protein deficits in adolescent and young adult rats at different levels: (1) impaired serotonergic (5-HT2A and 5-HT2C post-synaptic receptors) and GABAergic (GAD2 enzyme) signaling, and (2) decreased structural cytoskeletal neurofilament proteins (NF-H, NF-M and NF-L). Interestingly, these effects were not accompanied by an increase in apoptotic markers. In fact, chronic MDMA inhibited proteins of the apoptotic pathway (i.e., pro-apoptotic FADD, Bax and cytochrome c) leading to an inhibition of cell death markers (i.e., p-JNK1/2, cleavage of PARP-1) and suggesting regulatory mechanisms in response to the neurochemical changes caused by the drug. The data, together with the observed lack of GFAP activation, support the view that chronic MDMA effects, regardless of the rat developmental age, extends beyond neurotransmitter systems to impair other hippocampal structural cell markers. Interestingly, inhibitory changes in proteins from the apoptotic pathway might be taking place to overcome the protein deficits caused by MDMA.

García-Cabrerizo, R., & García-Fuster, M. J. (2015). Chronic MDMA induces neurochemical changes in the hippocampus of adolescent and young adult rats: Down-regulation of apoptotic markers. Neurotoxicology, 49, 104-113. http://dx.doi.org/10.1016/j.neuro.2015.06.001

Link to full text

MDMA for the treatment of mood disorder: all talk no substance?

June 1, 2015 / Depressive Disorders, MDMA, Papers, Psychology, Publications / By / ,

Abstract

BACKGROUND:

Unipolar depression is the third highest contributor to the global burden of disease, yet current pharmacotherapies typically take about 6 weeks to have an effect. A rapid-onset agent is an attractive prospect, not only to alleviate symptoms before first-line antidepressants display therapeutic action, but as a further treatment option in nonresponsive cases. It has been suggested that 3,4-methylene-dioxymethamphetamine (MDMA) could play a part in the treatment of depression, either as a rapid-onset pharmacological agent or as an adjunct to psychotherapy. Whilst these hypotheses are in keeping with the monoamine theory of depression and the principles surrounding psychotherapy, explicit experimental evidence of an antidepressant effect of MDMA has rarely been established.

AIMS:

To address the hypothesis surrounding MDMA as a rapid-onset antidepressant by examining pharmacological, psychological and behavioural studies. We consider whether this therapy could be safe by looking at the translation of neurotoxicity data from animals to humans.

METHOD:

A literature review of the evidence supporting this hypothesis was performed.

CONCLUSIONS:

The pharmacology of MDMA offers a promising target as a rapid-onset agent and MDMA is currently being investigated for use in psychotherapy in anxiety disorders; translation from these studies for use in depression may be possible. However, experimental evidence and safety analysis are insufficient to confirm or reject this theory at present.

Patel, R., & Titheradge, D. (2015). MDMA for the treatment of mood disorder: all talk no substance?. Therapeutic Advances in Psychopharmacology, 2045125315583786. https://dx.doi.org/10.1177/2045125315583786
Link to full text

Recreational 3,4-methylenedioxy-N-methylamphetamine (MDMA) or ‘ecstasy’ and self-focused compassion: Preliminary steps in the development of a therapeutic psychopharmacology of contemplative practices.

May 18, 2015 / MDMA, Papers, Psychology, Publications / By / , , , , , ,

Abstract

3,4-methylenedioxy-N-methylamphetamine (MDMA) produces diverse pro-social effects. Cognitive training methods rooted in Eastern contemplative practices also produce these effects through the development of a compassionate mindset. Given this similarity, we propose that one potential mechanism of action of MDMA in psychotherapy is through enhancing effects on intrapersonal attitudes (i.e. pro-social attitudes towards the self). We provide a preliminary test of this idea. Recreational MDMA (ecstasy) users were tested on two occasions, having consumed or not consumed ecstasy. Self-critical and self-compassionate responses to self-threatening scenarios were assessed before (T1) and after (T2) ecstasy use (or non-use), and then after compassionate imagery (T3). Moderating roles of dispositional self-criticism and avoidant attachment were examined. Separately, compassionate imagery and ecstasy produced similar sociotropic effects, as well as increases in self-compassion and reductions in self-criticism. Higher attachment-related avoidance was associated with additive effects of compassionate imagery and ecstasy on self-compassion. Findings were in line with MDMA’s neuropharmacological profile, its phenomenological effects and its proposed adjunctive use in psychotherapy. However, although conditions were balanced, the experiment was non-blind and MDMA dose/purity was not determined. Controlled studies with pharmaceutically pure MDMA are still needed to test these effects rigorously.

Kamboj, S. K., Kilford, E. J., Minchin, S., Moss, A., Lawn, W., Das, R. K., … & Freeman, T. P. (2015). Recreational 3, 4-methylenedioxy-N-methylamphetamine (MDMA) or ‘ecstasy’and self-focused compassion: Preliminary steps in the development of a therapeutic psychopharmacology of contemplative practices. Journal of Psychopharmacology, 0269881115587143.
Link to full text

MDMA for the treatment of mood disorder: all talk no substance?

May 1, 2015 / Depressive Disorders, MDMA, Neuroscience, Papers, Psychology, Publications / By / ,

Abstract

Background: Unipolar depression is the third highest contributor to the global burden of disease, yet current pharmacotherapies typically take about 6 weeks to have an effect. A rapid-onset agent is an attractive prospect, not only to alleviate symptoms before first-line antidepressants display therapeutic action, but as a further treatment option in nonresponsive cases. It has been suggested that 3,4-methylene-dioxymethamphetamine (MDMA) could play a part in the treatment of depression, either as a rapid-onset pharmacological agent or as an adjunct to psychotherapy. Whilst these hypotheses are in keeping with the monoamine theory of depression and the principles surrounding psychotherapy, explicit experimental evidence of an antidepressant effect of MDMA has rarely been established.

Aims: To address the hypothesis surrounding MDMA as a rapid-onset antidepressant by examining pharmacological, psychological and behavioural studies. We consider whether this therapy could be safe by looking at the translation of neurotoxicity data from animals to humans.

Method: A literature review of the evidence supporting this hypothesis was performed.

Conclusions: The pharmacology of MDMA offers a promising target as a rapid-onset agent and MDMA is currently being investigated for use in psychotherapy in anxiety disorders; translation from these studies for use in depression may be possible. However, experimental evidence and safety analysis are insufficient to confirm or reject this theory at present.

Patel, R., & Titheradge, D. (2015). MDMA for the treatment of mood disorder: all talk no substance?. Therapeutic Advances in Psychopharmacology, 2045125315583786. https://dx.doi.org/10.1177/2045125315583786

Link to full text

Intimate insight: MDMA changes how people talk about significant others

April 28, 2015 / MDMA, Papers, Psychology, Publications / By / , , ,

Abstract

Rationale: ±3,4-methylenedioxymethamphetamine (MDMA) is widely believed to increase sociability. The drug alters speech production and fluency, and may influence speech content. Here, we investigated the effect of MDMA on speech content, which may reveal how this drug affects social interactions.

Method: Thirty-five healthy volunteers with prior MDMA experience completed this two-session, within-subjects, double-blind study during which they received 1.5 mg/kg oral MDMA and placebo. Participants completed a five-minute standardized talking task during which they discussed a close personal relationship (e.g. a friend or family member) with a research assistant. The conversations were analyzed for selected content categories (e.g. words pertaining to affect, social interaction, and cognition), using both a standard dictionary method (Pennebaker’s Linguistic Inquiry and Word Count: LIWC) and a machine learning method using random forest classifiers.

Results: Both analytic methods revealed that MDMA altered speech content relative to placebo. Using LIWC scores, the drug increased use of social and sexual words, consistent with reports that MDMA increases willingness to disclose. Using the machine learning algorithm, we found that MDMA increased use of social words and words relating to both positive and negative emotions.

Conclusions: These findings are consistent with reports that MDMA acutely alters speech content, specifically increasing emotional and social content during a brief semistructured dyadic interaction. Studying effects of psychoactive drugs on speech content may offer new insights into drug effects on mental states, and on emotional and psychosocial interaction.

Baggott, M. J., Kirkpatrick, M. G., Bedi, G., & de Wit, H. (2015). Intimate insight: MDMA changes how people talk about significant others. Journal of Psychopharmacology, 0269881115581962. https://dx.doi.org/10.1177/0269881115581962
Link to full text

MDMA-assisted therapy: A new treatment model for social anxiety in autistic adults

March 25, 2015 / Anxiety Disorders / PTSD, MDMA, Papers, Psychology, Publications / By / , , ,

Abstract

The first study of 3,4-methylenedioxymethamphetamine (MDMA)-assisted therapy for the treatment of social anxiety in autistic adults commenced in the spring of 2014. The search for psychotherapeutic options for autistic individuals is imperative considering the lack of effective conventional treatments for mental health diagnoses that are common in this population. Serious Adverse Events (SAEs) involving the administration of MDMA in clinical trials have been rare and non-life threatening. To date, MDMA has been administered to over 1133 individuals for research purposes without the occurrence of unexpected drug-related SAEs that require expedited reporting per FDA regulations. Now that safety parameters for limited use of MDMA in clinical settings have been established, a case can be made to further develop MDMA-assisted therapeutic interventions that could support autistic adults in increasing social adaptability among the typically developing population. As in the case with classic hallucinogens and other psychedelic drugs, MDMA catalyzes shifts toward openness and introspection that do not require ongoing administration to achieve lasting benefits. This infrequent dosing mitigates adverse event frequency and improves the risk/benefit ratio of MDMA, which may provide a significant advantage over medications that require daily dosing. Consequently, clinicians could employ new treatment models for social anxiety or similar types of distress administering MDMA on one to several occasions within the context of a supportive and integrative psychotherapy protocol.

Danforth, A. L., Struble, C. M., Yazar-Klosinski, B., & Grob, C. S. (2015). MDMA-Assisted Therapy: A New Treatment Paradigm for Autistic Adults with Social Anxiety. Progress in Neuro-Psychopharmacology and Biological Psychiatry. http://dx.doi.org/10.1016/j.pnpbp.2015.03.011
Link to full text

Underground MDMA-, LSD- and 2-CB-assisted individual and group psychotherapy in Zurich: Outcomes, implications and commentary

March 24, 2015 / Anxiety Disorders / PTSD, LSD, MDMA, Papers, Psychology, Publications / By / ,

Abstract

Underground psychedelic-assisted psychotherapy has persisted in Europe despite the banning of the substances LSD and MDMA in the 1960s and 1980s, respectively. This article describes the work of a Zurich-based psychotherapist providing individual and group psycholytic psychotherapy, whose practice persisted for several years before she was arrested in 2009. The article provides commentary on the psychopharmacological, moral, ethical and legal issues of this case and discusses these issues in the context of the growing medical research of psychedelic substances as mainstream treatments for psychiatry.

Sessa, B., & Fischer, F. M. (2015). Underground MDMA-, LSD-and 2-CB-assisted individual and group psychotherapy in Zurich: Outcomes, implications and commentary. Drug Science, Policy and Law, 2, 1-8. https://dx.doi.org/10.1177/2050324515578080
Link to full text

Prosocial effects of MDMA: A measure of generosity

March 3, 2015 / MDMA, Papers, Psychology, Publications / By / , , ,

Abstract

Background: 3,4-methylenedioxymethamphetamine (MDMA) produces “prosocial” effects that contribute to its recreational use. Few studies have examined the cognitive and behavioral mechanisms by which MDMA produces these effects. Here we examined the effect of MDMA on a specific prosocial effect, i.e. generosity, using a task in which participants make decisions about whether they or another person will receive money (Welfare Trade-Off Task; WTT).

Methods: The project included one study without drug administration and one with MDMA. In Study 1, we administered the WTT to healthy adults (N = 361) and examined their performance in relation to measures of personality and socioeconomic status. In Study 2, healthy volunteers with MDMA experience (N = 32) completed the WTT after MDMA administration (0, 0.5, or 1.0 mg/kg).

Results: As expected, in both studies participants were more generous with a close friend than an acquaintance or stranger. In Study 1, WTT generosity was related to household income and trait Agreeableness. In Study 2, MDMA (1.0 mg/kg) increased generosity toward a friend but not a stranger, whereas MDMA (0.5 mg/kg) slightly increased generosity toward a stranger, especially among female participants.

Conclusions: These data indicate that the WTT is a valuable, novel tool to assess a component of prosocial behavior, i.e. generosity to others. The findings support growing evidence that MDMA produces prosocial effects, but, as with oxytocin, these appear to depend on the social proximity of the relationships. The brain mechanisms underlying the construct of generosity, or the effects of MDMA on this measure, remain to be determined.

Kirkpatrick, M., Delton, A. W., de Wit, H., & Robertson, T. E. (2015). Prosocial effects of MDMA: A measure of generosity. Journal of Psychopharmacology. https://dx.doi.org/10.1177/0269881115573806
Link to full text

What Can Neuroscience Tell Us About the Potential of Psychedelics in Healthcare?

February 23, 2015 / Ayahuasca, DMT, Iboga / Ibogaine, Ketamine, LSD, MDMA, Mescaline / Cacti, Mushrooms / Psilocybin, Neuroscience, Papers, Psychology, Publications / By /

Abstract

Health-related psychedelic research should focus on helping us flourish, not just remedying ill-health or addiction. We don’t know enough about how psychedelics could enhance human flourishing. Factors promoting health-through-flourishing include finding meaning in life, spiritual practices, comfortable levels of social bonds, emotionally/physically satisfying sex in a long-term monogamous relationship and control over one’s daily life. Psychedelic research could find more.Neuroscience anchors psychedelic research into disease and disorder, e.g. addiction, PSTD, migraine, anxiety, pain etc. Neurophenomenological psychedelics research could illuminate relationships between health, ASC/NOSCs and cognitive liberty to promote human flourishing. If we accept the self as an epiphenomenon of subsystems within the brain, we ‘know’ ‘unconsciously’, but are not aware of, many things which affect our lives profoundly. These include control over identifying, remembering and forgetting our states of mind and how to move between them. A prerequisite for integrated investigations into ASC/NOSCs is the establishment of a taxonomic knowledge base which lists, categorises and characterises ASC/NOSCs to enable us to choose specific states of mind and move securely among them. Or, in other words, to enable us to exercise our cognitive liberty safely.

I believe that human health and flourishing would be enhanced were we able to direct our states of being by consciously choosing them. Given the promise of mindfulness techniques to enhance our health, happiness and spiritual growth, constructing both personal and generic classifications of salient ASC/NOSCs makes sense. Laws need to change. The neuroscience of pleasure, love, spirituality, decision-making, pattern recognition and location of meaning should inform health-enhancing psychedelic research while promoting flourishing through cognitive liberty.

As part of cognitive liberty, our end-of-life choices should include how we die. In other words, our idea of the good death should include access to psychedelics. Dying high is increasingly likely to become a popular choice as baby boomers age and place their economic clout behind the reform of end-of-life laws as well as drug laws. Achieving such crucial legal changes depends partly on the ability to produce research to anchor evidence based law and policy. Research into psychedelics, ASC/NOSCs and the neurobiology of the dying process is essential.

Mackenzie, R. (2015). What can neuroscience tell us about the potential of psychedelics in healthcare? How the Neurophenomenology of Psychedelics Research Could Help us to Flourish Throughout Our Lives, as Well as to Enhance Our Dying. Current Drug Abuse Reviews, 7(3), 136-144. http://dx.doi.org/10.2174/1874473708666150107114927
Link to full text

Online Event - Psychedelic Care in Recreational Settings - 3 October 2024

REGISTER NOW
X

interested in becoming a trained psychedelic-assisted therapist?