Psychedelics Research Review: December 2020

Psychedelics Research Review: December 2020

Powered by

There was an incredible amount of research into psychedelics in 2020, providing empirical grounding for the Psychedelic Renaissance that is underway (see our Year in Review for more). Researchers certainly didn’t down tools in the month of December, with leading psychedelics researcher and head of Imperial College London’s Centre for Psychedelic Research Robin Carhart-Harris publishing his 100th output during the month.

We saw a number of research outputs published that sought to explore the setting element of the psychedelic experience. Gandy et al. reviewed the potential synergies between nature relatedness and psychedelic experiences, while Strickland et al. sought to understand the effects of the musical genre played during psilocybin sessions.

A piece by Cameron et al., published in Nature, described a non-hallucinogenic analog to ibogaine. The analog purportedly boasts similar therapeutic potential to ibogaine, but is non-toxic and non-hallucinogenic. This paper has encouraged healthy debate among psychedelics researchers and advocates, with some arguing the psychedelic experience is central to the efficacy of these therapies.

In a more meta piece, Forstmann and Sagioglou investigated how people perceive psychedelics researchers’ integrity and research quality. A number of other important pieces of research were published in December 2020, including an fMRI study of how LSD changes brain function over time; multiple studies on MDMA-assisted psychotherapy; and, a number of outputs pertaining to ketamine.

In our endeavour to provide you with the data necessary to track and analyse the emergent psychedelic sector, we’re working with Blossom Analysis to bring you a monthly research round-up.

Clicking the further analysis link will take you to a short summary of the work on Blossom’s website.

Jump to Article

The potential synergistic effects between psychedelic administration and nature contact for the improvement of mental health

Authors: Sam Gandy, Matthias Forstmann, Robin L. Carhart-HarrisChristopher Timmermann, David Luke & Rosalind Watts

Published: 6 December 2020

One-sentence summary: This review (2020) of the psychedelic therapy and nature relatedness argues that both may work in synergy and that maximising nature relatedness during psychedelic therapy could provide added benefits.

“Therapeutic psychedelic administration and contact with nature have been associated with the same psychological mechanisms: decreased rumination and negative affect, enhanced psychological connectedness and mindfulness-related capacities, and heightened states of awe and transcendent experiences, all processes linked to improvements in mental health amongst clinical and healthy populations. Nature-based settings can have inherently psychologically soothing properties which may complement all stages of psychedelic therapy (mainly preparation and integration) whilst potentiating increases in nature relatedness, with associated psychological benefits. Maximising enhancement of nature relatedness through therapeutic psychedelic administration may constitute an independent and complementary pathway towards improvements in mental health that can be elicited by psychedelics.“

Further analysis.

MDMA-facilitated cognitive-behavioural conjoint therapy for posttraumatic stress disorder: an uncontrolled trial

Authors: Candice M. Monson, et al.

Published: 7 December 2020

One-sentence summary: This open-label study (n=12, 6 couples) describes the safety, tolerability, and efficacy of MDMA (75-100mg) in combination with cognitive-behavioral conjoint therapy (CBCT) where one half of the couple was battling with PTSD.

“Cognitive-behavioural conjoint therapy (CBCT) for PTSD has been shown to improve PTSD, relationship adjustment, and the health and well-being of partners. MDMA (3,4-methylenedioxymethamphetamine) has been used to facilitate an individual therapy for PTSD. This study was an initial test of the safety, tolerability, and efficacy of MDMAfacilitated CBCT. Six couples with varying levels of baseline relationship satisfaction in which one partner was diagnosed with PTSD participated in a condensed version of the 15-session CBCT protocol delivered over 7 weeks. There were two sessions in which both members of the couple were administered MDMA. All couples completed the treatment protocol, and there were no serious adverse events in either partner. There were significant improvements in clinician-assessed, patient-rated, and partner-rated PTSD symptoms (pre- to post-treatment/follow-up effect sizes ranged from d = 1.85–3.59), as well as patient depression, sleep, emotion regulation, and trauma-related beliefs. In addition, there were significant improvements in patient and partner-rated relationship adjustment and happiness (d =.64–2.79). These results are contextualized in relation to prior results from individual MDMA-facilitated psychotherapy and CBCT for PTSD alone. MDMA holds promise as a facilitator of CBCT to achieve more robust and broad effects on individual and relational functioning in those with PTSD and their partners.“

Further analysis.

A non-hallucinogenic psychedelic analogue with therapeutic potential

Authors: Lindsay P. Cameron, et al.

Published: 9 December 2020

One-sentence summary: This paper describes an analog to ibogaine (tabernanthalog) with similar therapeutic potential that is non-toxic, and non-psychedelic.

The psychedelic alkaloid ibogaine has anti-addictive properties in both humans and animals1. Unlike most medications for the treatment of substance use disorders, anecdotal reports suggest that ibogaine has the potential to treat addiction to various substances, including opiates, alcohol and psychostimulants. The effects of ibogaine— like those of other psychedelic compounds—are long-lasting2, which has been attributed to its ability to modify addiction-related neural circuitry through the activation of neurotrophic factor signalling3,4. However, several safety concerns have hindered the clinical development of ibogaine, including its toxicity, hallucinogenic potential and tendency to induce cardiac arrhythmias. Here we apply the principles of function-oriented synthesis to identify the key structural elements of the potential therapeutic pharmacophore of ibogaine, and we use this information to engineer tabernanthalog—a water-soluble, non-hallucinogenic, non-toxic analogue of ibogaine that can be prepared in a single step. In rodents, tabernanthalog was found to promote structural neural plasticity, reduce alcohol- and heroin-seeking behaviour, and produce antidepressant-like effects. This work demonstrates that, through careful chemical design, it is possible to modify a psychedelic compound to produce a safer, non-hallucinogenic variant that has therapeutic potential.”

A day later two viewpoint articles (usually not featured) may be of interest in the context of this finding. ‘The Subjective Effects of Psychedelics Are Necessary for Their Enduring Therapeutic Effects‘ by David Yaden and Roland Griffiths, and ‘The Subjective Effects of Psychedelics May Not Be Necessary for Their Enduring Therapeutic Effects‘ by David Olson (co-author of the paper above).

Psychedelics in Psychiatry: Neuroplastic, Immunomodulatory, and Neurotransmitter Mechanisms

Authors: Antonio Inserra, Danilo De Gregorio & Gabriella Gobbi

Published online: 18 December 2020

One-sentence summary: This review presents the neurobiological therapeutic mechanisms by which psychedelics work, with a focus on outcomes on 1) neuroplasticity, 2) immune system, and 3) effects on neurotransmitter (-modulator) systems.

“Mounting evidence suggests safety and efficacy of psychedelic compounds as potential novel therapeutics in psychiatry. Ketamine has been approved by the Food and Drug Administration in a new class of antidepressants, and 3,4-methylenedioxymethamphetamine (MDMA) is undergoing phase III clinical trials for post-traumatic stress disorder. Psilocybin and lysergic acid diethylamide (LSD) are being investigated in several phase II and phase I clinical trials. Hence, the concept of psychedelics as therapeutics may be incorporated into modern society. Here, we discuss the main known neurobiological therapeutic mechanisms of psychedelics, which are thought to be mediated by the effects of these compounds on the serotonergic (via 5-HT2A and 5-HT1A receptors) and glutamatergic [via N-methyl-d-aspartate (NMDA) and α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors] systems. We focus on 1) neuroplasticity mediated by the modulation of mammalian target of rapamycin-, brain-derived neurotrophic factor-, and early growth response-related pathways; 2) immunomodulation via effects on the hypothalamic-pituitary-adrenal axis, nuclear factor ĸB, and cytokines such as tumor necrosis factor-α and interleukin 1, 6, and 10 production and release; and 3) modulation of serotonergic, dopaminergic, glutamatergic, GABAergic, and norepinephrinergic receptors, transporters, and turnover systems. We discuss arising concerns and ways to assess potential neurobiological changes, dependence, and immunosuppression. Although larger cohorts are required to corroborate preliminary findings, the results obtained so far are promising and represent a critical opportunity for improvement of pharmacotherapies in psychiatry, an area that has seen limited therapeutic advancement in the last 20 years. Studies are underway that are trying to decouple the psychedelic effects from the therapeutic effects of these compounds.

LSD alters dynamic integration and segregation in the human brain

Authors: Andrea I. Luppi, Robin L. Carhart-HarrisLeor Roseman, Ioannis Pappas, David K. Menon & Emanuel A. Stamatakisa

Published online: 19 December 2020

One-sentence summary: This fMRI study (2020) improves our understanding of how LSD changes brain function over time and how subjective effects (e.g. ego dissolution) map onto these changes.

“Investigating changes in brain function induced by mind-altering substances such as LSD is a powerful method for interrogating and understanding how mind interfaces with brain, by connecting novel psychological phenomena with their neurobiological correlates. LSD is known to increase measures of brain complexity, potentially reflecting a neurobiological correlate of the especially rich phenomenological content of psychedelic-induced experiences. Yet although the subjective stream of consciousness is a constant ebb and flow, no studies to date have investigated how LSD influences the dynamics of functional connectivity in the human brain. Focusing on the two fundamental network properties of integration and segregation, here we combined graph theory and dynamic functional connectivity from resting-state functional MRI to examine time-resolved effects of LSD on brain networks properties and subjective experiences. Our main finding is that the effects of LSD on brain function and subjective experience are non-uniform in time: LSD makes globally segregated sub-states of dynamic functional connectivity more complex, and weakens the relationship between functional and anatomical connectivity. On a regional level, LSD reduces functional connectivity of the anterior medial prefrontal cortex, specifically during states of high segregation. Time-specific effects were correlated with different aspects of subjective experiences; in particular, ego dissolution was predicted by increased small-world organisation during a state of high global integration. These results reveal a more nuanced, temporally-specific picture of altered brain connectivity and complexity under psychedelics than has previously been reported.“

A comparison of MDMA-assisted psychotherapy to non-assisted psychotherapy in treatment-resistant PTSD: A systematic review and meta-analysis

Authors: Benjamin J. G. Illingworth, Declan J. Lewis, Andrew T. Lambarth, Kate Stocking, James M. N. Duffy, Luke A. Jelen & James J. Rucker

Published: 20 December 2020

One-sentence summary: This systematic review and meta-analysis of MDMA-assisted therapy for PTSD, found that over four RCT’s (n=67), PTSD scores (CAPS-IV) were lower in the 75mg and 125mg groups (not 100mg), and depression scores (BDI) only in the 75mg group.

Rationale: Novel, evidence-based treatments are required for treatment-resistant post-traumatic stress disorder (PTSD). 3,4-Methylenedioxymethamphetamine (MDMA) has beneficially augmented psychotherapy in several small clinical trials. Objective: To review the use of MDMA-assisted psychotherapy in treatment-resistant PTSD. Methods: Systematic searches of four databases were conducted from inception to February 2020. A meta-analysis was performed on trials which were double-blinded, randomised, and compared MDMA-assisted psychotherapy to psychotherapy and placebo. The primary outcomes were the differences in Clinician Administered PTSD Scale (CAPS-IV) score and Beck’s Depression Inventory (BDI). Secondary outcome measures included neurocognitive and physical adverse effects, at the time, and within 7 days of intervention. Results: Four randomised controlled trials (RCTs) met inclusion criteria. When compared to active placebo, intervention groups taking 75 mg (MD -46.90; 95% (confidence intervals) CI -8.78, -5.02), 125 mg (MD -20.98; 95% CI -34.35, -7.61) but not 100 mg (MD -12.90; 95% CI -36.09, 10.29) of MDMA with psychotherapy, had significant decreases in CAPS-IV scores, as did the inactive placebo arm (MD -33.20; 95% CI -40.53, -25.87). A significant decrease in BDI when compared to active placebo (MD -10.80; 95% CI -20.39, -1.21) was only observed at 75 mg. Compared to placebo, participants reported significantly more episodes of low mood, nausea and jaw-clenching during sessions and lack of appetite after 7 days. Conclusion: These results demonstrate potential therapeutic benefit with minimal physical and neurocognitive risk for the use of MDMA-assisted psychotherapy in TR-PTSD, despite little effect on Beck’s Depression Inventory. Better powered RCTs are required to investigate further.”

How psychedelic researchers’ self-admitted substance use and their association with psychedelic culture affect people’s perceptions of their scientific integrity and the quality of their research

Authors: Matthias Forstmann & Christina Sagioglou

Published: 25 December 2020

One-sentence summary: A three-part survey study (n=952) found that psychedelic use by (fictitious) researchers themselves led to lower ratings on integrity, but not the quality of research.

“Across three studies (total N = 952), we tested how self-admitted use of psychedelics and association with psychedelic culture affects the public’s evaluation of researchers’ scientific integrity and of the quality of their research. In Studies 1 and 2, we found that self-admitted substance use negatively affected people’s assessment of a fictitious researcher’s integrity (i.e. being unbiased, professional, and honest), but not of the quality of his research, or how much value and significance they ascribed to the findings. Study 3, however, found that an association with psychedelic culture (i.e. presenting work at a scientific conference that includes social activities stereotypically associated with psychedelic culture) negatively affected perceived research quality (e.g. less valid, true, unbiased). We further found that the latter effect was moderated by participants’ personal experience with psychedelic substances: only participants without such experience evaluated research quality more negatively when it was presented in a stereotyped context.”

Further analysis.

Set and Setting: A Randomized Study of Different Musical Genres in Supporting Psychedelic Therapy

Authors: Justin C. Strickland, Albert Garcia-Romeu & Matthew W. Johnson

Published: 29 December 2020

One-sentence summary: This further analysis of an open-label, counter-balanced study (n=10) with psilocybin (20-30mg/70kg) found that overtone-based music (e.g. gongs) was more effective than classical music (for smoking cessation, mystical experience – but only trends – very small sample size).

“Mounting evidence supports the serotonin 2A receptor agonist psilocybin as a psychiatric pharmacotherapy. Little research has experimentally examined how session “set and setting” impacts subjective and therapeutic effects. We analyzed the effects of the musical genre played during sessions of a psilocybin study for tobacco smoking cessation. Participants (N = 10) received psilocybin (20–30 mg/70 kg) in two sessions, each with a different musical genre (Western classical versus overtone-based), with the order counterbalanced. Participants chose one genre for a third session (30 mg/70 kg). Mystical experiences scores tended to be higher in overtone-based sessions than in Western classical sessions. Six of ten participants chose the overtone-based music for a third session. Biologically confirmed smoking abstinence was similar based on musical choice, with a slight benefit for participants choosing the overtone-based playlist (66.7% versus 50%). These data call into question whether Western classical music typically used in psychedelic therapy holds a unique benefit. Broadly, we call for experimentally examining session components toward optimizing psychedelic therapeutic protocols.“

Further analysis.

More Psychedelic Research Papers

Use CTRL/CMD+F to quickly search if anything relevant for you has been published this month.

Join our Newsletter

Get the latest research updates sent to your inbox.