What is PTSD?
Post Traumatic Stress Disorder (PTSD) is a condition that can arise when a person experiences a traumatic or life-threatening event. In these situations our body activates its fight or flight response to respond quickly and accordingly by either fending off the threat or fleeing the dangerous situation. However depending on genetic predisposition and the severity of the trauma some survivors are left with lasting effects on their brain’s ability to properly utilize this response as well as a dysfunctional fear extinction mechanism.
Veterans returning from the battlefield are particularly prone to this type of illness and it continues to be a growing issue as more soldiers return from their deployment. Symptoms of PTSD include flashbacks, hypersensitivity or the feeling of being “on edge”, as well as avoidance behaviors especially of situations and things that remind the patient of the trauma. Typically antidepressants and other prescription drugs such as Valium were used to treat PTSD but ultimately these drugs do not solve the problem leading many of these patients to addiction and suicide especially when combined with alcohol.
The Science Behind Why Cannabis Works for PTSD
Cannabis can be an invaluable tool to these patients because its primary constituent THC acts on cannabinoid receptors in the brain. These receptors assist in an important function that is damaged in these patients, the ability to forget. The following clip from the film “The Botany of Desire” describes this somewhat counterintuitive evolutionary adaptation:
The endocannabinoid system (ECS), specifically CB1 receptors, mediate this action in the brain. THC acts as a partial agonist at these receptors eliciting a cascade of cell signaling responses that lead to a rescue of fear extinction learning. CB1 receptors are found primarily in the central nervous system and are found in most of the brain but particularly the action of these receptors in the prefrontal cortex, hippocampus, and the amygdala are what make cannabis so useful for PTSD. These receptors are responsible for maintaining hedonia (state of well-being) as well as opposing hypothalamus pituitary axis (HPA) response to stress, bringing the body back to homeostasis following exposure to stressful stimuli.
There has been a large amount of preclinical data gathered that implicates the ECS as a primary target for the treatment of PTSD. A study from 2002 led by Marsicano shows that the CB1 receptors in the amygdala are required for the extinction of fear memories. A further study by Hill in 2005 showed that following chronic stress signaling in the ECS is downregulated. This downregulation impaired reversal learning (the ability to be trained differently to two stimuli based on reward or punishment response) in mice and as anticipated induced perservatory behaviors. The study also found that the effects of chronic stress were reversed when an exogenous CB1 agonist was applied.
Human studies using positron emission tomography (PET) scans have revealed that the CB1 receptors of PTSD patients are primarily unoccupied suggesting a deficiency in endocannabinoid signaling. In addition, blood endocannabinoid concentrations in PTSD patients were considerably lower than those that had not experienced trauma. Further human studies published in 2013 in the journal Neurobiology of Learning and Memory confirmed that THC’s action at the CB1 receptor facilitated fear extinction learning through its interactions with the amygdala, ventromedial prefrontal cortex (vmPFC), and hippocampus.
Recently the federal government has lightened its chokehold on cannabinoid research for PTSD. Last March in an unprecedented move, the DEA gave the University of Arizona the green light to study cannabis use in veterans with the disorder. This approval marks a huge accomplishment for researchers who have had to maneuver a variety of obstacles the federal government has implemented.
The Endocannabinoid System in Stress-Related Psychiatric Illness
What is the endocannabinoid system (ECS)?
For centuries cannabis has been used for relief from stress and anxiety suggesting that the compounds found in the plant regulate the body’s stress response, and in fact that’s just what researchers are finding. The endocannabinoid system (ECS) is a system of receptors and molecules that regulate a variety of responses in our bodies. These cannabinoid receptors coined CB1 and CB2 are like special locks only allowing the binding of molecules with specific configurations called endocannabinoids (eCBs). Cannabinoids produced in the cannabis plant can also bind to these receptors, producing a similar, but longer-lived effect than eCBs. The binding of these compounds to these receptors induces eCB signaling which serves as a means to buffer the body’s stress response.
How does the endocannabinoid system work?
Following exposure to stressful environments eCBs are released into the synapse, the space between two neuronal connections. Here they bind to cannabinoid receptors, causing the release of neurotransmitters to be inhibited in that particular neuron (presynaptic neuron).
The ECS could be compared to your brain’s climate control. When too much activity is occurring in the brain your ECS kicks in and quiets this activity, bringing levels back to base line. This eCB signaling occurs in a retrograde (backwards) fashion meaning the eCB is released from the post-synaptic neuron and acts on the cannabinoid receptors of the pre-synaptic neuron. Ultimately, this leads to an overall decrease in neurotransmitter release, quieting this activity.
The ECS and its relationship to depression and anxiety
The action of eCBs at cannabinoid receptors has been implicated in variety of mood and stress related illnesses such as depression and PTSD. To study how these receptors play a role in these disorders researchers created mice lacking the cannabinoid receptor CB1. These mice exhibit increased anxiety suggesting that these receptors are important for regulating these behaviors. Additional support for this idea came from the observation that increased levels of eCBs in blood is associated with reduced anxiety and depression while lowered levels have the opposite effect. Based on studies of these mice and the observation that cannabis alleviates stress, researchers believed that cannabinoid receptors could be an ideal target for the treatment of PTSD. They found that when they stimulated these receptors in models of PTSD using compounds similar to THC there was a significant improvement in symptoms, confirming their hunch.
Further confirmation of the involvement of cannabinoid receptors in depression and anxiety came about because of a weight loss drug that came to market in 2006 called Rimonabant. Rimonabant acts by blocking the CB1 receptor causing a significant reduction in eCB signaling. Though the drug worked well for weight loss it was promptly removed from the market after it resulted in numerous reports of severe anxiety, depression, and in some cases suicide.
Taken together, this data shows that the ECS plays a critical role in the regulation the body’s stress response with deficient eCB levels being associated with anxiety behaviors and depression, while elevated levels of eCBs are associated with reduced anxiety and stress. Through this deeper understanding of the ECS researchers can now focus on developing new compounds that act on this system to alleviate and hopefully cure some of these debilitating ailments.
Source: Hill, 2013. "Translational evidence for the involvement of the endocannabinoid system in stress-related psychiatric illnesses" Biol Mood Anxiety Disord. 2013; 3: 19.
SC Laboratories President Josh Wurzer will be giving two presentations at the conference on Wednesday. His first presentation will cover the basics of the cannabinoids, the body’s endocannabinoid system, and the therapeutic potential of the endocannabinoid system in a variety of ailments. His second presentation will cover the importance of laboratory testing and the methods involved in screening cannabis for potency, pesticides, residual solvents, and terpene content.
The Marijuana for Medical Purposes Conference organized by the International Pharmaceutical Academy, will be held September 16–17, 2014 in Toronto, Canada. This conference will assemble the top minds in medical marijuana to discuss every aspect of the industry. Participants of the conference will gain valuable knowledge of the best global practices for the business, technology, science, research, laws and regulations of medical marijuana in Canada. Established and outdated mindsets regarding cannabinoids will be challenged with up to date knowledge and research, and experts will offer a forecast of the next 3–5 years for the industry.
For more info about the Marijuana for Medical Purposes Conference check out their website at the following link: http://www.ipacanada.com/Marihuana_Medical_Purposes_2014/
SC Labs President and Co-Founder Joshua Wurzer to speak at Harvard Medical School
It’s conference season and this year Massachusetts-based Medicinal Genomics is bringing together the best and brightest in cannabis for CannMed 2016, a two-day event at Harvard Medical School. Keynote speakers include Raphael Mechoulam, the researcher who discovered THC and Orrin Devinsky, the lead investigator in GW Pharmaceuticals trials using Epidolex for Dravet Syndrome.
The conference comes at a unique time as the advent of sequencing technology has enabled personalized medicine allowing for a better understanding of the genetic regulation of the endocannabinoid system. Conference topics include the use of cannabinoid therapeutics in neurological disorders and the role of the endocannabinoid system in such disorders.
SC Laboratories President Joshua Wurzer will also be presenting a lecture entitled “Chemotypic and Quality Control Analysis of the California Medical Cannabis Market.” Medicinal Genomics also plans to present their hypothesis on the current state of the testing market and its potential impact on the diversity of the cannabis microbiome.
Where: The Joseph B. Martin Conference Center at the Harvard School of Medicine, Boston, MA
When: April 10-11, 2016
More info at: http://www.medicinalgenomics.com/cannmed2016/