Terrence McKenna famously proposed the Stoned Ape Theory which suggests that psychedelic mushrooms catalyzed human evolution by enhancing visual acuity (low dose), sexual activity (moderate dose), and visionary experience (high dose). Moreover, he believed that the fungi likely brought about self-reflection and language. This article looks at new evidence that lends further support to the vital role that psilocybin might have played in human evolution.
There are numerous critical periods throughout the maturation of a human. For example, there are developmental periods during which language is most readily learned, physical sensations are developed, emotional responses are mastered, and movement is refined. The enhanced neuroplasticity that allows for these critical periods doesn't last forever, so once a period is passed it's especially difficult to learn a new skill. This hypothesis posits that psychedelics may temporarily reinstate this plasticity, sensitizing adults to environmental inputs and facilitating the relearning process that can be optimized via psychotherapy.
Ketamine can address both physical and psychological pain. In fact, it's widely used as an analgesic. Many people with depression also experience physical pain. This study found that ketamine had a stronger antidepressant effect in patients with treatment-resistant depression (TRD) and pain than in patients with TRD alone.
After languishing for decades from legal restrictions and stigma, research into psychedelic drugs is exploding – with the encouragement of the Food and Drug Administration. Recent clinical trial successes suggest some long-banned drugs could soon be authorized as treatments for debilitating illnesses. Yet because of these drugs’ history, FDA approval would be just one important step in a complex process to transform these compounds into therapies. Incorporating psychedelic drugs into clinical practice will require peeling back multiple layers of legal prohibition, clarifying prescribing guidelines, and developing treatment models that work for drug-makers, physicians, and payers.
Background: Treatment resistant depression (TRD) is defined as a major depressive episode that does not improve in response to at least two trials, each of a different class, of antidepressant medication. Pharmacotherapy of TRD with low dose ketamines has been shown as relatively successful in recent studies. Effects of such pharmacotherapy can be augmented by combining ketamine with psychotherapeutic interventions such as Zdyb’s Therapeutic Reset of Internal Processes (TRIP) protocol. Method: 10 adult TRD patients (4 men, 6 women) were treated with low dose ketamines and were also receiving psychotherapeutic intervention as per TRIP protocol. All patients were administered the Patient Health Questionnaire, module 9 (PHQ9) which is a measure of a major depressive episode. The PHQ9 was administered twice: on baseline (i.e., prior to treatment) and after the treatment. Results: On average, our patients fell in the moderate range of severity with respect to symptoms of TRD at baseline (pre-TRIP) as by their mean PHQ9 score of 17.9, (SD = 5.1). Their mean PHQ9 score decreased post TRIP treatment to 9.5 (SD = 6.6): the difference is significant in a t-test, t(10) = 4.3172, p = 0002 (two-tailed). The magnitude of the decrease amounts to 46.9% of the average baseline score. Discussion and Conclusions: Our patients experienced significant reductions in symptoms of TRD in this pilot study. Research studies are now needed with control groups of TRD patients on a waiting list or also of those receiving only the ketamine pharmacotherapy
Previous research showed acute psychedelic effects were associated with decreases in racial trauma (RT) symptoms among black, indigenous, and people of color (BIPOC). Among samples comprised primarily of white participants, positive outcomes of psychedelic experiences have been mediated by increases in psychological flexibility. Therefore, we examined whether changes in psychological flexibility from before to after a psychedelic experience mediated the relationship between acute psychedelic effects and changes in RT symptoms among BIPOC.
Promising initial data indicate that the glutamate N-methyl-D-aspartate (NMDA) receptor antagonist ketamine may be beneficial in post-traumatic stress disorder (PTSD). Here, we explore the neural correlates of ketamine-related changes in PTSD symptoms, using a rich battery of functional imaging data (two emotion-processing tasks and one task-free scan), collected from a subset of participants of a randomized clinical trial of repeated-dose intravenous ketamine vs midazolam (total N = 21). In a pre-registered analysis, we tested whether changes in an a priori set of imaging measures from a target neural circuit were predictive of improvement in PTSD symptoms, using leave-one-out cross-validated elastic-net regression models (regions of interest in the target circuit consisted of the dorsal and rostral anterior cingulate cortex, ventromedial prefrontal cortex, anterior hippocampus, anterior insula, and amygdala). Improvements in PTSD severity were associated with increased functional connectivity between the ventromedial prefrontal cortex (vmPFC) and amygdala during emotional face-viewing (change score retained in model with minimum predictive error in left-out subjects, standardized regression coefficient [β] = 2.90). This effect was stronger in participants who received ketamine compared to midazolam (interaction β = 0.86), and persisted following inclusion of concomitant change in depressive symptoms in the analysis model (β = 0.69). Improvement following ketamine was also predicted by decreased dorsal anterior cingulate activity during emotional conflict regulation, and increased task-free connectivity between the vmPFC and anterior insula (βs = −2.82, 0.60). Exploratory follow-up analysis via dynamic causal modelling revealed that whilst improvement in PTSD symptoms following either drug was associated with decreased excitatory modulation of amygdala→vmPFC connectivity during emotional face-viewing, increased top-down inhibition of the amygdala by the vmPFC was only observed in participants who improved under ketamine. Individuals with low prefrontal inhibition of amygdala responses to faces at baseline also showed greater improvements following ketamine treatment. These preliminary findings suggest that, specifically under ketamine, improvements in PTSD symptoms are accompanied by normalization of hypofrontal control over amygdala responses to social signals of threat.