Cannabis Science & Technology - June 2022

Cannabis Science & Technology - June 2022

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Psychedelics: New Frontiers in Alternative Medicine | vol. 5 no. | cannabissciencetech.com 22 feature / research The amygdala is part of the lim- bic system, a network of interconnect- ed structures responsible for emotion and behavioral responses to stimu- li and events. The amygdala activates the "fight or flight" response when we encounter danger or feel unsafe. Fight or flight is a survival response to both physical and emotional danger. Once the amygdala is triggered, messag- es are sent to the frontal lobes for eval- uation. The frontal lobes are respon- sible for executive function. This area of the brain can evaluate the stimulus and determine an appropriate response, which includes overriding the amyg- dala's survival response. If the amyg- dala does activate the fight or flight response, the limbic system then acti- vates multiple physiological systems, in- cluding the sympathetic nervous sys- tem, which stimulates the release of a It is within this system adrenaline (ep- inephrine) and norepinephrine, as well as other stress hormones (1). It is within this system and during this process that memories and associated emotions are stored in the brain. This is why PTSD and depression are closely related with respect to how the messages are coded, stored, and accessed. With depression, the brain has trouble accessing joy asso- ciated with memories, whereas traumat- ic experiences are encoded with nega- tive emotions; both require rewiring. Trauma is an extreme form of emo- tional response to a distressing experi- ence often caused by a sudden or unpre- dictable event (1). As we have seen and experienced with the COVID-19 pan- demic, no one is able to avoid traumat- ic events. Trauma affects us all, and we each respond differently. Traumat- ic events include but are not limited to: the loss of a loved one, a violent situa- tion, physical abuse, a car accident, or military combat experience. The trau- ma is stored in the brain, and when these memories are triggered, they can undermine a person's sense of safety and trigger hypervigilance (1). Once trauma is stored in the brain, it manifests in numerous ways. It can be subtle or obvious and often destruc- tive. How someone responds to trau- ma is determined by multiple factors in- cluding past experiences, the type of event, the developmental stage and pro- cesses of the person experiencing the event, and the social and cultural envi- ronment. Manifestations or symptoms of depression or PTSD can include emo- tional struggles, sleep disturbances, an- ger issues, difficulty with profession- al or personal relationships, and even physical pain. Living in a high stress de- fense mode can then lead to "Amygdala Hijack" which is when the amygdala dis- ables the frontal lobe and takes control or "hijacks" the brain. Previous models of how the brain processes experience theorized that we receive stimuli from our environ- ment, process the stimuli in higher functioning areas of the brain, and send out the signals with an appropriate re- sponse (12). However, new research sug- gests that the brain predicts what each unique situation or environmental mod- el will be based on prior similar sensory inputs instead of each individual experi- ence, a "predictive coding" theory. This is a way for the brain to function more efficiently when processing new infor- mation. When errors occur the brain corrects for the prediction error and ad- justs the model. Andrew Clark, a cogni- tive scientist at the University of Edin- burgh in Edinburgh, Scotland said: "You experience, in some sense, the world that you expect to experience," (12). Therapeutic analysis of a drug is ob- served based on an absorption, dis- tribution, metabolism, and excretion (ADME) profile to understand and pre- dict how the drug will work. With re- spect to FDA-approved drugs like ket- amine, this data is widely accessible. However, for drugs such as cannabis or psilocybin, which are currently Sched- ule I drugs, research is limited, mak- ing it difficult to fully understand how the drugs work. Psilocybin is most com- monly ingested orally as a raw mush- room, a capsule of powder, or as a pow- der mixed with food or tea. Psilocybin is absorbed in the gut and metabolized by the liver in first pass metabolism, and then its most prevalent area of known action into the body is through the 5HT 2A serotonin receptors (13). Once ingested, understanding of how the drug works therapeutically is limit- ed. Research and clinical trials are need- ed to discover how psilocybin works in the brain. Neural imaging indicates that psilocybin and psychedelics appear to ac- tivate all areas of the brain, a crucial fac- tor in understanding why and how psilo- cybin works. Evidence also suggests that psilocybin has an exemplary safety pro- file with few harmful side effects, particu- larly when microdosing. When adverse side effects do occur, they appear to be re- lated to 5HT 2A receptor problems, or re- ports of the classic "bad trip," which can be frightening in the moment, but dis- appear when the drug wears off. Howev- er, people with a history of mental illness, such as schizophrenia or bipolar disorder should be thoroughly screened, and work closely with medical professionals if they are considering psychedelic therapy. Current knowledge of how psilocy- bin works is predicated on an under- standing of the "predictive coding" model of how the brain processes ex- periences and the role of the amygdala and the amygdala "hijack" process. Four key concepts that lead to the successful treatment of depression and PTSD with psilocybin therapy are: neuroplastici- ty of the brain, the "Default Mode Net- work," rewiring of synapses and path- ways, and surrendering control. Neuroplasticity means the brain is malleable and can be reformed, adapted,

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