Research on Cannabis & ketamine as Medicine and Psychedelic
Cannabis
Articles on Cannabis and Archeology:
https://www.sapiens.org/column/curiosities/archaeology-marijuana/?
https://psychedelicreview.com/is-cannabis-a-psychedelic-drug/
https://jcannabisresearch.biomedcentral.com/articles/10.1186/s42238-020-00032-2
https://thefreshtoast.com/cannabis/cannabis-and-ketamine-is-there-a-risk-of-interaction/?amp=1
Rabinak, C. A., Blanchette, A., Zabik, N. L., Peters. C., Marusak, H. A., Iadipaolo, A., Elrahal, F. (2020). Cannabinoid modulation of corticolimbic activation to threat in trauma-exposed adults: a preliminary study, Psychopharmacology (Berl), 237(6), p. 1813-1826.
Results: In adults with PTSD, THC lowered threat-related amygdala reactivity, increased mPFC activation during threat, and increased mPFC-amygdala functional coupling.
Conclusions: These preliminary data suggest that THC modulates threat-related processing in trauma-exposed individuals with PTSD, which may prove advantageous as a pharmacological approach to treating stress- and trauma-related psychopathology.
Raymundi, A. M., da Silva, T. R., Sohn, J., Bertoglio, L. J., & Stern, C. A. (2020). Effects of ∆9-tetrahydrocannabinol on aversive memories and anxiety: a review from human studies. BMC psychiatry, 20(1), 420.
Results: At low doses, THC can enhance the extinction rate and reduce anxiety responses. Both effects involve the activation of cannabinoid type-1 receptors in discrete components of the corticolimbic circuitry, which could couterbalance the low “endocannabinoid tonus” reported in PTSD patients. The advantage of associating CBD with THC to attenuate anxiety while minimizing the potential psychotic or anxiogenic effect produced by high doses of THC has been reported. The effects of THC either alone or combined with CBD on aversive memory reconsolidation, however, are still unknown.
Conclusions: Current evidence from healthy humans and PTSD patients supports the THC value to suppress anxiety and aversive memory expression without producing significant adverse effects if used in low doses or when associated with CBD. Future studies are guaranteed to address open questions related to their dose ratios, administration routes, pharmacokinetic interactions, sex-dependent differences, and prolonged efficacy.
LaFrance, E., M., Glodosky, N., C., Bonn-Miller, M., Cuttler, C. (2020). Short and Long-Term Effects of Cannabis on Symptoms of Post-Traumatic Stress Disorder, Journal of Affective Disorders, 274, p. 298-304.
All symptoms were reduced by more than 50% immediately after cannabis use. Time predicted larger decreases in intrusions and irritability, with later cannabis use sessions predicting greater symptom relief than earlier sessions. Higher doses of cannabis predicted larger reductions in intrusions and anxiety, and dose used to treat anxiety increased over time. Baseline severity of all symptoms remained constant across time.
Limitations : The sample was self-selected, self-identified as having PTSD, and there was no placebo control group.
Conclusions : Cannabis provides temporary relief from PTSD-related symptoms. However, it may not be an effective long-term remedy as baseline symptoms were maintained over time and dose used for anxiety increased over time, which is indicative of development of tolerance.
Abrams, D., I. (2018). The therapeutic effects of Cannabis and cannabinoids: An update from the National Academies of Sciences, Engineering and Medicine report, European Journal of Internal Medicine, (49), 7-11.
……the report concluded that there was conclusive or substantial evidence that Cannabis or cannabinoids are effective for the treatment of pain in adults; chemotherapy-induced nausea and vomiting and spasticity associated with multiple sclerosis. Moderate evidence was found for secondary sleep disturbances. The evidence supporting improvement in appetite, Tourette syndrome, anxiety, posttraumatic stress disorder, cancer, irritable bowel syndrome, epilepsy and a variety of neurodegenerative disorders was described as limited, insufficient or absent. A chapter of the NASEM report enumerated multiple barriers to conducting research on Cannabis in the US that may explain the paucity of positive therapeutic benefits in the published literature to date.
Baker, D., Pryce, G., Giovannoni, G., Thompson, A., J. (2003). The therapeutic potential of cannabis, The Lancet Neurology, 2(5), Volume 2, Issue 5, 291-298.
Research of the cannabinoid system has many similarities with that of the opioid system. In both instances, studies into drug-producing plants led to the discovery of an endogenous control system with a central role in neurobiology. Few compounds have had as much positive press from patients as those of the cannabinoid system. While these claims are investigated in disorders such as multiple sclerosis spasticity and pain, basic research is discovering interesting members of this family of compounds that have previously unknown qualities, the most notable of which is the capacity for neuroprotection. Large randomised clinical trials of the better known compounds are in progress. Even if the results of these studies are not as positive as many expect them to be, that we are only just beginning to appreciate the huge therapeutic potential of this family of compounds is clear.
Abizaid, A., Merali, Z., & Anisman, H. (2019). Cannabis: A potential efficacious intervention for PTSD or simply snake oil?. Journal of psychiatry & neuroscience : JPN, 44(2), 75–78.
“The limited research in humans has nevertheless suggested that cannabis can ameliorate particular features of PTSD. However, these studies had a small number of participants, did not distinguish between the conditions that promoted the disorder (e.g., an acute traumatic experience, chronic stressor encounters, multiple trauma experiences), and did not consider the time at which the disorder was treated relative to when the trauma was experienced. In effect, the studies were typically of low quality, and large-scale studies remain to be conducted evaluating the efficacy of cannabis use in the treatment of PTSD”
Historical references to cannabis being a psychedelic
Ketamine
Peer reviewed papers
Mandal, S., Sinha, V. K., & Goyal, N. (2019). Efficacy of ketamine therapy in the treatment of depression. Indian journal of psychiatry, 61(5), 480–485. https://doi.org/10.4103/psychiatry.IndianJPsychiatry_484_18
Zheng, W., Zhou, Y. L., Liu, W. J., Wang, C. Y., Zhan, Y. N., Li, H. Q., Chen, L. J., Li, M. D., & Ning, Y. P. (2018). Rapid and longer-term antidepressant effects of repeated-dose intravenous ketamine for patients with unipolar and bipolar depression. Journal of psychiatric research, 106, 61–68. https://doi.org/10.1016/j.jpsychires.2018.09.013
Singh, J. B., Fedgchin, M., Daly, E., Xi, L., Melman, C., De Bruecker, G., Tadic, A., Sienaert, P., Wiegand, F., Manji, H., Drevets, W. C., & Van Nueten, L. (2016). Intravenous Esketamine in Adult Treatment-Resistant Depression: A Double-Blind, Double-Randomization, Placebo-Controlled Study. Biological psychiatry, 80(6), 424–431. https://doi.org/10.1016/j.biopsych.2015.10.018
DiazGranados, N., Ibrahim, L. A., Brutsche, N. E., Ameli, R., Henter, I. D., Luckenbaugh, D. A., Machado-Vieira, R., & Zarate, C. A., Jr (2010). Rapid resolution of suicidal ideation after a single infusion of an N-methyl-D-aspartate antagonist in patients with treatment-resistant major depressive disorder. The Journal of clinical psychiatry, 71(12), 1605–1611. https://doi.org/10.4088/JCP.09m05327blu
Murrough, J. W., Iosifescu, D. V., Chang, L. C., Al Jurdi, R. K., Green, C. E., Perez, A. M., Iqbal, S., Pillemer, S., Foulkes, A., Shah, A., Charney, D. S., & Mathew, S. J. (2013). Antidepressant efficacy of ketamine in treatment-resistant major depression: a two-site randomized controlled trial. The American journal of psychiatry, 170(10), 1134–1142. https://doi.org/10.1176/appi.ajp.2013.13030392
Shin, C., & Kim, Y. K. (2020). Ketamine in Major Depressive Disorder: Mechanisms and Future Perspectives. Psychiatry investigation, 17(3), 181–192. https://doi.org/10.30773/pi.2019.0236
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