Natural Psychoplastogens As Antidepressant Agents
Abstract
Benko, J., & Vranková, S. (2020). Natural Psychoplastogens As Antidepressant Agents. Molecules, 25(5), 1172., https://doi.org/10.3390/molecules25051172
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Benko, J., & Vranková, S. (2020). Natural Psychoplastogens As Antidepressant Agents. Molecules, 25(5), 1172., https://doi.org/10.3390/molecules25051172
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3,4-Methylenedioxymethamphetamine (MDMA)-assisted psychotherapy for posttraumatic stress disorder (PTSD) has been shown to significantly reduce clinical symptomatology, but posttraumatic growth (PTG), which consists of positive changes in self-perception, interpersonal relationships, or philosophy of life, has not been studied with this treatment. Participant data (n = 60) were pooled from three Phase 2 clinical studies employing triple-blind crossover designs. Participants were required to meet DSM-IV-R criteria for PTSD with a score higher than 50 on the Clinician-Administered PTSD Scale (CAPS-IV) as well as previous inadequate response to pharmacological and/or psychotherapeutic treatment. Data were aggregated into two groups: an active MDMA dose group (75-125 mg of MDMA; n = 45) or placebo/active control (0-40 mg of MDMA; n = 15). Measures included the Posttraumatic Growth Inventory (PTGI) and the CAPS-IV, which were administered at baseline, primary endpoint, treatment exit, and 12-month follow-up. At primary endpoint, the MDMA group demonstrated more PTG, Hedges’ g = 1.14, 95% CI [0.49, 1.78], p < .001; and a larger reduction in PTSD symptom severity, Hedges’ g = 0.88, 95% CI [-0.28, 1.50], p < .001, relative to the control group. Relative to baseline, at the 12-month follow-up, within-subject PTG was higher, p < .001; PTSD symptom severity scores were lower, p < .001; and two-thirds of participants (67.2%) no longer met criteria for PTSD. MDMA-assisted psychotherapy for PTSD resulted in PTG and clinical symptom reductions of large-magnitude effect sizes. Results suggest that PTG may provide a new mechanism of action warranting further study.
Gorman, I., Belser, A. B., Jerome, L., Hennigan, C., Shechet, B., Hamilton, S., Yazar-Klosinski, B., Emerson, A., & Feduccia, A. A. (2020). Posttraumatic Growth After MDMA-Assisted Psychotherapy for Posttraumatic Stress Disorder. Journal of traumatic stress, 33(2), 161–170. https://doi.org/10.1002/jts.22479
Though there was initial interest in the use of psychedelic drugs for psychiatric treatment, bad outcomes and subsequent passage of the Substance Act of 1970, which placed psychedelic drugs in the Schedule I category, significantly limited potential progress. More recently, however, there has been renewal in interest and promise of psychedelic research. The purpose of this review is to highlight contemporary human studies on the use of select psychedelic drugs, such as psilocybin, LSD, MDMA and ayahuasca, in the treatment of various psychiatric illnesses, including but not limited to treatment-resistant depression, post-traumatic stress disorder, end-of-life anxiety, and substance use disorders. The safety and efficacy as reported from human and animal studies will also be discussed. Accumulated research to date has suggested the potential for psychedelics to emerge as breakthrough therapies for psychiatric conditions refractory to conventional treatments. However, given the unique history and high potential for misuse with popular distribution, special care and considerations must be undertaken to safeguard their use as viable medical treatments rather than drugs of abuse.
Chi, T., & Gold, J. A. (2020). A review of emerging therapeutic potential of psychedelic drugs in the treatment of psychiatric illnesses. Journal of the Neurological Sciences, 116715., 10.1016/j.jns.2020.116715
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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.
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.
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.
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
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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.
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.
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.
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
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4-Iodo-2,5-dimethoxy-N-(2-methoxybenzyl)phenethylamine (25I-NBOMe), commonly called “N-Bomb,” is a synthetic phenethylamine with psychedelic and entactogenic effects; it was available on the Internet both as a legal alternative to lysergic acid diethylamide (LSD) and as a surrogate of 3,4-methylenedioxy-methamphetamine (MDMA), but now it has been scheduled among controlled substances. 25I-NBOMe acts as full agonist on serotonergic 5-HT2A receptors. Users are often unaware of ingesting fake LSD, and several cases of intoxication and fatalities have been reported. In humans, overdoses of “N-Bomb” can cause tachycardia, hypertension, seizures, and agitation. Preclinical studies have not yet widely investigated the rewarding properties and behavioral effects of this compound in both sexes. Therefore, by in vivo microdialysis, we evaluated the effects of 25I-NBOMe on dopaminergic (DA) and serotonergic (5-HT) transmissions in the nucleus accumbens (NAc) shell and core, and the medial prefrontal cortex (mPFC) of male and female rats. Moreover, we investigated the effect of 25I-NBOMe on sensorimotor modifications as well as body temperature, nociception, and startle/prepulse inhibition (PPI). We showed that administration of 25I-NBOMe affects DA transmission in the NAc shell in both sexes, although showing different patterns; moreover, this compound causes impaired visual responses in both sexes, whereas core temperature is heavily affected in females, and the highest dose tested exerts an analgesic effect prominent in male rats. Indeed, this drug is able to impair the startle amplitude with the same extent in both sexes and inhibits the PPI in male and female rats. Our study fills the gap of knowledge on the behavioral effects of 25I-NBOMe and the risks associated with its ingestion; it focuses the attention on sex differences that might be useful to understand the trend of consumption as well as to recognize and treat intoxication and overdose symptoms.
Miliano, C., Marti, M., Pintori, N., Castelli, M. P., Tirri, M., Arfè, R., & De Luca, M. A. (2019). Neurochemical and Behavioral Profiling in Male and Female Rats of the Psychedelic Agent 25I-NBOMe. Frontiers in Pharmacology, 10., 10.3389/fphar.2019.01406
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