OPEN Foundation

Menu
Search
Close this search box.

OPEN Foundation

In vivo effects of 3,4-methylenedioxymethamphetamine (MDMA) and its deuterated form in rodents: Drug discrimination and thermoregulation.

January 13, 2020 / Anxiety Disorders / PTSD, MDMA, Papers, Pharmacology & Chemistry, Psychiatry & Medicine, Publications / By / , , ,

Abstract

BACKGROUND:

Recent clinical studies support the use of 3,4-methylenedioxymethamphetamine (MDMA) as an adjunct treatment for posttraumatic stress disorder (PTSD). Despite these promising findings, MDMA administration in controlled settings can increase blood pressure, heart rate, and body temperature. Previous studies indicate thatO-demethylated metabolites of MDMA contribute to its adverse effects. As such, limiting the conversion of MDMA to reactive metabolites may mitigate some of its adverse effects and potentially improve its safety profile for therapeutic use.

METHODS:

We compared the interoceptive and hyperthermic effects of a deuterium-substituted form of MDMA (d2-MDMA) to MDMA using rodent drug discrimination and biotelemetry procedures, respectively.

RESULTS:

Compared to MDMA, d2-MDMA produced full substitution for a 1.5 mg/kg MDMA training stimulus with equal potency and effectiveness in the drug discrimination experiment. In addition, d2-MDMA produced increases in body temperature that were shorter-lasting and of lower magnitude compared to equivalent doses of MDMA. Last, d2-MDMA and MDMA were equally effective in reversing the hypothermic effects of the selective 5-HT2A/2C antagonist ketanserin.

CONCLUSION:

These findings indicate that deuterium substitution of hydrogen at the methylenedioxy ring moiety does not impact MDMA’s interoceptive effects, and compared to MDMA, d2-MDMA has less potential for producing hyperthermic effects and likely has similar pharmacodynamic properties. Given that d2-MDMA produces less adverse effects than MDMA, but retains similar desirable effects that are thought to relate to the effective treatment of PTSD, additional investigations into its effects on cardiovascular functioning and pharmacokinetic properties are warranted.

Berquist, M. D., Leth-Petersen, S., Kristensen, J. L., & Fantegrossi, W. E. (2020). In vivo effects of 3, 4-methylenedioxymethamphetamine (MDMA) and its deuterated form in rodents: drug discrimination and thermoregulation. Drug and Alcohol Dependence, 107850., 10.1016/j.drugalcdep.2020.107850
Link to full text

Antidepressant and neurocognitive effects of serial ketamine administration versus ECT in depressed patients

January 13, 2020 / Depressive Disorders, Ketamine, Neuroscience, Papers, Psychiatry & Medicine, Publications / By / , , , , , ,

Abstract

BACKGROUND:

While electroconvulsive therapy (ECT) is considered the gold standard for acute treatment of patients with otherwise treatment-resistant depression, ketamine has recently emerged as a fast-acting treatment alternative for these patients. Efficacy and onset of action are currently among the main factors that influence clinical decision making, however, the effect of these treatments on cognitive functions should also be a crucial point, given that cognitive impairment in depression is strongly related to disease burden and functional recovery. ECT is known to induce transient cognitive impairment, while little is known about ketamine’s impact on cognition. This study therefore aims to compare ECT and serial ketamine administration not only with regard to their antidepressant efficacy but also to acute neurocognitive effects.

METHODS:

Fifty patients suffering from depression were treated with either serial ketamine infusions or ECT. Depression severity and cognitive functions were assessed before, during, and after treatment.

RESULTS:

ECT and ketamine administration were equally effective, however, the antidepressant effects of ketamine occurred faster. Ketamine improved neurocognitive functioning, especially attention and executive functions, whereas ECT was related to a small overall decrease in cognitive performance.

CONCLUSIONS:

Due to its pro-cognitive effects and faster antidepressant effect, serial ketamine administration might be a more favorable short-term treatment option than ECT.

LIMITATIONS:

As this research employed a naturalistic study design, patients were not systematically randomized, there was no control group and patients received concurrent and partially changing medications during treatment.

CLINICAL TRIALS REGISTRATION:

Functional and Metabolic Changes in the Course of Antidepressive Treatment, https://clinicaltrials.gov/ct2/show/NCT02099630, NCT02099630.

Basso, L., Bönke, L., Aust, S., Gärtner, M., Heuser-Collier, I., Otte, C., … & Grimm, S. (2020). Antidepressant and neurocognitive effects of serial ketamine administration versus ECT in depressed patients. Journal of Psychiatric Research.,  10.1016/j.jpsychires.2020.01.002

Link to full text 

A Dangerous Method? Psychedelic Therapy at Modum Bad, Norway, 1961-76

January 13, 2020 / Anxiety Disorders / PTSD, Ayahuasca, Depressive Disorders, LSD, Mushrooms / Psilocybin, Papers, Psychology, Publications / By /

Abstract

After many years of disregard, the use of psychedelic drugs in psychiatric treatment has re-emerged in recent years. The prospect that psychedelics may again be integrated into mainstream psychiatry has aroused interest in long-forgotten research and experience from the previous phase of psychedelic therapy, which lasted from the late 1940s to the 1970s. This article will discuss one large-scale psychedelic therapy programme at Modum Bad Nervesanatorium, a psychiatric clinic which treated 379 inpatients with psychedelic drugs during the years 1961-76. The psychiatrists there initially regarded the psychedelic treatment as efficacious and without serious negative reactions, but reports of long-term harm have since surfaced. This article discusses how insights from Modum Bad might benefit the new generation of psychedelic treatment efforts.
Johnstad, P. G. (2020). A dangerous method? Psychedelic therapy at Modum Bad, Norway, 1961–76. History of Psychiatry, 31(2), 217-226., https://doi.org/10.1177%2F0957154X19894537
Link to full text

Ayahuasca’s ‘afterglow’: improved mindfulness and cognitive flexibility in ayahuasca drinkers.

January 11, 2020 / Ayahuasca, Papers, Psychology, Publications / By / ,

Abstract

RATIONALE:
There is a growing body of evidence demonstrating the therapeutic potential of ayahuasca for treating depression and anxiety. However, the mechanisms of action involved in ayahuasca’s therapeutic effects are unclear. Mindfulness and cognitive flexibility may be two possible psychological mechanisms. Like other classic psychedelics, ayahuasca also leads to an ‘afterglow’ effect of improved subjective well-being that persists after the acute effects have subsided. This period may offer a window of increased therapeutic potential.
OBJECTIVE:
To explore changes in mindfulness and cognitive flexibility before and within 24 h after ayahuasca use.METHODS:
Forty-eight participants (54% female) were assessed on measures of mindfulness (Five Facets Mindfulness Questionnaire (FFMQ)), decentering (Experiences Questionnaire (EQ)), and cognitive flexibility (Cognitive Flexibility Scale (CFS)), and completed the Stroop and Wisconsin Picture Card Sorting Task (WPCST) before drinking ayahuasca, and again within 24 h.
RESULTS:
Mindfulness (FFMQ total scores and four of the five mindfulness facets: observe, describe, act with awareness, and non-reactivity) and decentering (EQ) significantly increased in the 24 h after ayahuasca use. Cognitive flexibility (CFS and WPCST) significantly improved in the 24 h after ayahuasca use. Changes in both mindfulness and cognitive flexibility were not influenced by prior ayahuasca use.
CONCLUSIONS:
The present study supports ayahuasca’s ability to enhance mindfulness and further reports changes in cognitive flexibility in the ‘afterglow’ period occur, suggesting both could be possible psychological mechanisms concerning the psychotherapeutic effects of ayahuasca. Given psychological gains occurred regardless of prior ayahuasca use suggests potentially therapeutic effects for both naïve and experienced ayahuasca drinkers.
Murphy-Beiner, A., & Soar, K. (2020). Ayahuasca’s ‘afterglow’: improved mindfulness and cognitive flexibility in ayahuasca drinkers. Psychopharmacology, 1-9., https://doi.org/10.1007/s00213-019-05445-3
Link to full text

Long-term follow-up of psilocybin-assisted psychotherapy for psychiatric and existential distress in patients with life-threatening cancer.

January 9, 2020 / Anxiety Disorders / PTSD, Depressive Disorders, Mushrooms / Psilocybin, Papers, Psychology, Publications / By / , , , , , ,

Abstract

BACKGROUND:
A recently published randomized controlled trial compared single-dose psilocybin with single-dose niacin in conjunction with psychotherapy in participants with cancer-related psychiatric distress. Results suggested that psilocybin-assisted psychotherapy facilitated improvements in psychiatric and existential distress, quality of life, and spiritual well-being up to seven weeks prior to the crossover. At the 6.5-month follow-up, after the crossover, 60-80% of participants continued to meet criteria for clinically significant antidepressant or anxiolytic responses.
METHODS:
The present study is a long-term within-subjects follow-up analysis of self-reported symptomatology involving a subset of participants that completed the parent trial. All 16 participants who were still alive were contacted, and 15 participants agreed to participate at an average of 3.2 and 4.5 years following psilocybin administration.
RESULTS:
Reductions in anxiety, depression, hopelessness, demoralization, and death anxiety were sustained at the first and second follow-ups. Within-group effect sizes were large. At the second (4.5 year) follow-up approximately 60-80% of participants met criteria for clinically significant antidepressant or anxiolytic responses. Participants overwhelmingly (71-100%) attributed positive life changes to the psilocybin-assisted therapy experience and rated it among the most personally meaningful and spiritually significant experiences of their lives.
CONCLUSION:
These findings suggest that psilocybin-assisted psychotherapy holds promise in promoting long-term relief from cancer-related psychiatric distress. Limited conclusions, however, can be drawn regarding the efficacy of this therapy due to the crossover design of the parent study. Nonetheless, the present study adds to the emerging literature base suggesting that psilocybin-facilitated therapy may enhance the psychological, emotional, and spiritual well-being of patients with life-threatening cancer.
Agin-Liebes, G. I., Malone, T., Yalch, M. M., Mennenga, S. E., Ponté, K. L., Guss, J., … & Ross, S. (2020). Long-term follow-up of psilocybin-assisted psychotherapy for psychiatric and existential distress in patients with life-threatening cancer. Journal of Psychopharmacology, 0269881119897615., https://doi.org/10.1177%2F0269881119897615
Link to full text

Anxiety-like behavior induced by salicylate depends on age and can be prevented by a single dose of 5-MeO-DMT

September 17, 2024 / 5-MeO-DMT, Anxiety Disorders / PTSD, Neuroscience, Papers, Substance / Leave a Comment / By / , , , , , , ,

Abstract

Salicylate intoxication is a cause of tinnitus and comorbidly associated with anxiety in humans. In a previous work, we showed that salicylate induces anxiety-like behavior and hippocampal type 2 theta oscillations (theta2) in mice. Here we investigate if the anxiogenic effect of salicylate is dependent on age and previous tinnitus experience. We also tested whether a single dose of DMT can prevent this effect. Using microwire electrode arrays, we recorded local field potential in young (4-5- month-old) and old (11-13-month-old) mice to study the electrophysiological effect of tinnitus in the ventral hippocampus (vHipp) and medial prefrontal cortex (mPFC) in an open field arena and elevated plus maze 1h after salicylate (300mg/kg) injection. We found that anxiety-like behavior and increase in theta2 oscillations (4-6 Hz), following salicylate pre-treatment, only occurs in young (normal hearing) mice. We also show that theta2 and slow gamma oscillations increase in the vHipp and mPFC in a complementary manner during anxiety tests in the presence of salicylate. Finally, we show that pre-treating mice with a single dose of the hallucinogenic 5-MeO-DMT prevents anxiety-like behavior and the increase in theta2 and slow gamma oscillations after salicylate injection in normal hearing young mice. This work further support the hypothesis that anxiety-like behavior after salicylate injection is triggered by tinnitus and require normal hearing. Moreover, our results show that hallucinogenic compounds can be effective in treating tinnitus-related anxiety.

Winne, J., Boerner, B. C., Malfatti, T., Brisa, E., Doerl, J., Nogueira, I., Leão, K. E., & Leão, R. N. (2020). Anxiety-like behavior induced by salicylate depends on age and can be prevented by a single dose of 5-MeO-DMT. Experimental neurology, 326, 113175. https://doi.org/10.1016/j.expneurol.2020.113175

Link to full text

A qualitative descriptive analysis of effects of psychedelic phenethylamines and tryptamine

January 7, 2020 / DMT, MDMA, Mushrooms / Psilocybin, Papers, Psychology, Publications / By / ,

Abstract

OBJECTIVE:

The number of novel psychedelic phenethylamines and tryptamines has continued to increase, but little academic research has focused on the effects of these substances. We sought to determine and compare the subjective effects of various substances.

METHODS:

We conducted in-depth interviews with 39 adults (75.4% male and 87.2% White) who reported experience using psychedelic phenethylamines and/or tryptamines. Participants described the effects of compounds they have used. We examined the subjective drug effects in a qualitative descriptive manner.

RESULTS:

Participants reported on the use of 36 compounds. The majority (64.1%) reported the use of 2C series drugs, with 2C-B use being most prevalent; 38.5% reported the use of NBOMe, and 25.6% reported the use of DOx. With regard to tryptamines, 46.2% reported use, and 4-AcO-DMT was the most prevalent drug used in this class. 2C-B was often described as being more favorable than other 2C series compounds with the effects described as being comparable with MDMA and LSD. NBOMe effects were generally described in an unfavorable manner, and the effects of DOx were often described as lasting too long (12-36 hr). The effects of 4-AcO-DMT were often described as mimicking psilocybin.

CONCLUSION:

Knowing the effects of various compounds can inform education, prevention, and harm reduction efforts regarding the use of these drugs.

Palamar, J. J., & Acosta, P. (2020). A qualitative descriptive analysis of effects of psychedelic phenethylamines and tryptamines. Human Psychopharmacology: Clinical and Experimental, e2719., 10.1002/hup.2719
Link to full text

Correlation between the potency of hallucinogens in the mouse head-twitch response assay and their behavioral and subjective effects in other species

January 7, 2020 / DMT, LSD, Neuroscience, Papers, Psychology, Publications / By / , , , ,

Abstract

Serotonergic hallucinogens such as lysergic acid diethylamide (LSD) induce head twitches in rodents via 5-HT2A receptor activation. The goal of the present investigation was to determine whether a correlation exists between the potency of hallucinogens in the mouse head-twitch response (HTR) paradigm and their reported potencies in other species, specifically rats and humans. Dose-response experiments were conducted with phenylalkylamine and tryptamine hallucinogens in C57BL/6J mice, enlarging the available pool of HTR potency data to 41 total compounds. For agents where human data are available (n = 36), a strong positive correlation (r = 0.9448) was found between HTR potencies in mice and reported hallucinogenic potencies in humans. HTR potencies were also found to be correlated with published drug discrimination ED50 values for substitution in rats trained with either LSD (r = 0.9484, n = 16) or 2,5-dimethoxy-4-methylamphetamine (r = 0.9564, n = 21). All three of these behavioral effects (HTR in mice, hallucinogen discriminative stimulus effects in rats, and psychedelic effects in humans) have been linked to 5-HT2A receptor activation. We present evidence that hallucinogens induce these three effects with remarkably consistent potencies. In addition to having high construct validity, the HTR assay also appears to show significant predictive validity, confirming its translational relevance for predicting subjective potency of hallucinogens in humans. These findings support the use of the HTR paradigm as a preclinical model of hallucinogen psychopharmacology and in structure-activity relationship studies of hallucinogens. Future investigations with a larger number of test agents will evaluate whether the HTR assay can be used to predict the hallucinogenic potency of 5-HT2A agonists in humans.

Halberstadt, A. L., Chatha, M., Klein, A. K., Wallach, J., & Brandt, S. D. (2020). Correlation between the potency of hallucinogens in the mouse head-twitch response assay and their behavioral and subjective effects in other species. Neuropharmacology, 107933., 10.1016/j.neuropharm.2019.107933
Link to full text

The experimental effects of psilocybin on symptoms of anxiety and depression: A meta-analysis.

January 2, 2020 / Anxiety Disorders / PTSD, Depressive Disorders, Mushrooms / Psilocybin, Papers, Psychology, Publications / By / , , , ,

Abstract

The current meta-analysis examined the effects of psilocybin in combination with behavioral interventions on anxiety and depression in samples with elevated symptoms. Across four studies (one uncontrolled; three randomized, placebo-controlled; N = 117), within-group pre-post and pre-follow-up effects on anxiety and depression were large (Hedges’ gs=1.16 to 1.47) and statistically significant. Across three placebo-controlled studies, pre-post placebo-controlled effects were also large (gs = 0.82 to 0.83) and statistically significant. No serious adverse events were reported. Limitations include the small number of studies and risk for bias within studies. Results tentatively support future research on psilocybin for the treatment of anxiety and depression.

Goldberg, S. B., Pace, B. T., Nicholas, C. R., Raison, C. L., & Hutson, P. R. (2020). The experimental effects of psilocybin on symptoms of anxiety and depression: A meta-analysis. Psychiatry Research, 112749., https://doi.org/10.1016/j.psychres.2020.112749
Link to full text

[Neuroscientific and psychological explanations for the therapeutic effects of psychedelics]

January 1, 2020 / Papers, Psychology, Publications / By /

Abstract

Psychedelics have a strong therapeutic potential for the treatment of biomedical disorders, but the working mechanisms underlying psychedelics are only poorly understood.<br/> AIM: To discuss different mechanisms underlying the therapeutic effects of classic psychedelics.<br/> METHOD: To make a distinction between different levels of explanation: the pharmacological, the neurocognitive and the psychological level.<br/> RESULTS: At the pharmacological level, classic psychedelics affect via the serotonin-receptor, the production of glutamate and brain-derived neurotrophic factor (bdnf), which stimulate neurogenesis. Psychedelics also have anti-flammatory properties and thereby have a protective effect on the brain. At the neurocognitive level, psychedelics have been associated with a reduced activation of the default mode network, which has been implicated in self-referential processing and rumination. At the same time, the brain’s entropy increases, reflected in an increased connectivity between different brain areas. At the psychological level, the therapeutic efficacy of psychedelics has been attributed to the mystical experience, as well as to its awe-inducing potential, the feelings of connectedness and an enhanced awareness of emotions.<br/> CONCLUSION: Psycholytic and psychedelic therapy act at different levels, but ultimately the combination of different mechanisms will help us to understand how psychedelics – in the right set and setting – can be used successfully in therapeutic practice.
van Elk, M. (2020). Neuroscientific and psychological explanations for the therapeutic effects of psychedelics. Tijdschrift Voor Psychiatrie, 62(8), 677-683., https://pubmed.ncbi.nlm.nih.gov/32816296/
Link to full text

interested in becoming a trained psychedelic-assisted therapist?

Indigenous Talk: Fulni-ô Culture & Jurema - Online Event - Dec 12th

REGISTER NOW