Authored by @joeylittle. For many, marijuana has become the self-medication drug of choice when it comes to addressing a multitude of PTSD symptoms. But are there ways in which cannabis may be doing more harm than good? This article will take a look into both the benefits and risks involved in using marijuana--legal or otherwise--to manage PTSD. MARIJUANA: WHAT IS IT, AND HOW DOES IT WORK? Marijuana is the common name for what we will refer to as cannabis. Cannabis is a psychoactive drug used all over the world for recreation, pain management, spiritual/religious ceremonies, and, lately, as an adjunct treatment for various illnesses including multiple cancers, epilepsy, and mental health issues. It is derived primarily from the plants Cannabis sativa, and Cannabis indica. Cannabis works through chemical compounds called cannibinoids, which are able to interface with the cannabinoid receptors we (and most animals) have on certain cells in the body. Receptor cells are located in areas of the brain (type 1, or CB1) and the immune system (type 2, or CB2). There are 483 known chemical compounds in the Cannabis plant, but so far only 84 have been recognized as cannabinoids. Of those, there are four principle compounds that make cannabis have the specific, desired effects it has. They are: THC (Tetrohydrocannabinol) – this is the main psychoactive chemical found in cannabis. THC was identified in 1964 by a team led by Israeli chemist Dr. Rafael Mechoulam, and is responsible for causing euphoria, altered visual and auditory senses, and even schizophrenia-like psychoses. Other effects include increased appetite, mild analgesic properties, decreased aggression, decreased vomiting/nausea, impaired motor skills, diminished short-term and working memory, and fatigue. The most common way to describe the “strength” of cannabis is by referencing THC content. The synthetic formulation, dronabinol (Marinol), is generally prescribed to relieve nausea, pain, and vomiting for cancer patients undergoing chemotherapy. CBD (Cannabidiol) is a non-psychoactive chemical that acts as an antagonist to THC, meaning that it blocks many of the undesirable psychosis effects of THC. It also has been proven to relieve inflammation, nausea, anxiety, and convulsions. CBD has been identified as having the ability to shut down the gene that is linked to metastasis in breast cancer, and is currently in human medical trials in order to become approved for that use. CBN (Cannabinol) is mainly a by-product of THC degradation due to exposure to light and air. It is not very present in the living plant, but increases as the plant degrades in storage after harvest. CBN has mild psychoactive properties, and, due to a selective affinity for certain receptors, can be an effective immunosuppressant. Although it is legally an analogue of THC, cannabinol is not scheduled as a psychotropic substance. It is the model for the synthetic cannabinoid known as nabilone (Cesamet), prescribed primarily for pain relief and nausea. Nabilone has also been used in preliminary studies investigating cannabinoid treatment for PTSD symptoms. THCV, THV (Tetrahydrocannabivarin) is very similar to THC, yet has the effect of reducing the psychoactive properties of cannabis. It is found to greater or lesser degrees in the cannabis plant, and most specifically in cannabis indica, which is native to Asia. It is not scheduled as a psychotropic substance. There are three primary methods of cannabis consumption: smoking, vaporizing, and ingesting. In clinical trials, cannabis is also administered in precise chemical proportions intravenously. Smoking cannabis has many downsides. When combusted, there are 111 separate chemical compounds that can be identified in the smoke gas (which is what one inhales). Of those, only 12% are cannabinoids. The remaining 88% are mostly various residues. Of those, a significant portion are polycyclic aromatic hydrocarbons (PAH). Seven PAH are currently classified as human carcinogens, and five of those seven are identified within cannabis smoke. The common practice of holding the smoke in the lungs to increase the effects of the drug is a myth – bio-availability of cannabinoids occurs within the first few seconds of inhaling – and so, holding the smoke in the lungs does nothing but allow more time for the absorption of the residue compounds, including the carcinogens. Cannabis smoking is 50-70% more toxic than smoking nicotine. Inhaling cannabis as a vaporized gas (“vaping”) significantly reduces the creation of additional chemical compounds. The vaporized gas consists of 95% cannabinoids (as opposed to the 12% found in smoke gas), and the remaining 5% is made up of trace amounts of one PAH and plant oils. The associated risk with vaping involves the access to a greater concentration of the drug, specifically to increased levels of THC - which is the compound responsible for psychosis when taken in high amounts. Ingesting cannabis as a pill or oil creates no exposure to PAHs. However, the absorption rate differs greatly. In a study done specifically on the bio-availability of THC in pill form vs. vaporized cannabis, it was determined that the vapor was effective for pain management within 15 minutes, while the pill form took between 60 and 90 minutes to take effect. While the pill did continue to reduce pain hours after the vapor had worn off, the pill has the downside of being very difficult (even dangerous) to self-adjust the dosage. The psychoactive effects between the two were similar. There have been reported difficulties with managing the bio-availability in the two most common cannabis pills, the synthetics nabilone and dronabinol; for this reason they are becoming less and less prescribed, especially as cannabis for medical use has become more legal in north America and elsewhere. A spray, nabiximols (Sativex) has proven to be more effective, likely because it is derived from a number of organic cannabinoids instead of one or two synthesized analogues. However, it is currently mainly available only in Europe and Asia, and only as a drug to be prescribed for controlling the spasticity in multiple sclerosis. It is currently undergoing trials in the US and elsewhere for use by those in cancer treatment. Eating the dried and prepared plant provides a slow bio-availability and inconsistent dosing but is an utterly non-toxic way of receiving the drug. Some cannabinoids are only activated by heat, and consuming raw cannabis may or may not produce the same effects as cannabis that has been properly heated. Cannabinoids are also not soluable in water, so any attempt to create a 'tea' must involve a fatty liquid such as milk. THE IMPACT OF LEGALIZATION IN THE US Twenty-three US states (Alaska, Arizona, California, Colorado, Connecticut, Delaware, Hawai’i, Illinois, Maine, Maryland, Massachusetts, Michigan, Minnesota, Montana, Nevada, New Hampshire, New Jersey, New Mexico, New York, Oregon, Rhode Island, Vermont, and Washington), and the District of Columbia have legalized cannabis for medical use. Of those, three (OR, WA, CO) have legalized it for recreational use as well. ** Cannabis is becoming big business. ArcView, an investment and research group, has been commissioned by various stakeholders in the growing cannabis industry to report on the evolution of legalization in the US and predict how the market might grow. In 2013, the US market for legal cannabis was worth 1.5 billion USD. In 2014, it was worth 2.7 billion USD. The ArcView report indicates that the rise in value will continue steadily, that 16 more states will make cannabis use legal--14 recreationally and 2 medically--and that the value of the market will rise and stabilize at 11 billion USD annually by 2020, just five short years from now. The availability of legal cannabis will allow research to expand. Currently, in the US, the only supplier for legal research cannabis is the University of Mississippi. This arrangement was put in place by the US government in 1968 – and scientists still need to apply for their supply of the plant (with the hybridization they specify) through various governmental agencies, after which those agencies will give permission to the university to grow it and then deliver it back to the study requesting it. Obtaining cannabis for research has been time and labor intensive. The expansion of legality will allow for more and different kinds of research and studies to flourish. Of course, we already have data from studies made over the last 40 years. It is slow-going, as with any research trial, for it is only possible to study only one aspect of the drug at a time. Much more is understood about the analgesic and anti-emetic properties of cannabis. Using the drug in its organic (non-synthesized) form, with the combinations of cannabinoids that naturally occur, has been a significant source of relief for cancer sufferers enduring the pain and nausea caused by chemotherapy. The way in which cannabis stimulates appetite is also helpful for people whose suffering makes it impossible for them to eat. But what about PTSD? USING CANNABIS FOR PTSD A PTSD sufferer is likely to see the potential benefits in cannabis use. Adults suffering from PTSD are three times more likely to be dependent on cannabis, and the statistics for military veterans are generally higher. There is strong anecdotal evidence as well as preliminary scientific evidence supporting that cannabis or its synthetic derivatives may address hyper-arousal, anxiety, sleep disturbance, nightmares, and depression. But cannabis use is not without risks. Recent studies have confirmed the links between the downgrading of cannabinoid receptors in the brain and regular cannabis use. In short, introducing external THC creates change in the brain that results in dependence on the drug. The good news is, this change appears to reverse approximately four weeks after discontinuing cannabis use. While dependence is not inherently bad, it goes hand in hand with requiring increasing amounts – as the body loses CB1 receptors, more THC is needed to create the desired effect - and higher levels of THC directly correspond with the increased risk of psychosis. There is a link being established between THC-induced psychosis and schizophrenia, which may ultimately point to an effective treatment for that illness, but right now, little is understood except that there are neurological correlations. Additionally, a very recent study with a large (2,391) sample group showed consistent findings in cannabis use preceding mania. This study has provided the groundwork for research into a causal relationship between mania and cannabis. What is clear is that anyone with a current or suspected bipolar diagnosis is putting themselves at risk for inducing a manic episode when they ingest THC. So far, most of the dialogue around cannabis for PTSD has been focused on symptom management. The effect of cannabis on PTSD treatment is a different conversation altogether. A 2011 published longitudinal study set out to examine the affect cannabis use disorder (CUD) had on PTSD symptoms over the course of an inpatient stay. The average length of stay was 78 days, and the patients were male military vets. The results showed that the subjects with a CUD who discontinued use during treatment experienced little to no change in symptoms, while those subjects without a CUD experienced more improvement than was expected. “These findings, in combination with prior work, highlight a possible bidirectional relation between PTSD and problematic cannabis use. Indeed, individuals with PTSD may be especially likely to use cannabis to alleviate particular PTSD symptoms in the short term, but long-term use for these reasons may in fact lead to dependence, the treatment of which may actually inhibit, rather than promote, recovery from PTSD. Future work would benefit from further elucidating the short- and long-term bidirec- tional nature of the relation between cannabis use and related disorders and PTSD symptomatology.” (Prospective Investigation of the Impact of Cannabis Use Disorders on Posttraumatic Stress Disorder Symptoms Among Veterans in Residential Treatment, Psychological Trauma: Theory, Research, Practice, and Policy In the public domain 2013, Vol. 5, No. 2, 193–200) MEDICAL MARIJUANA, SYNTHETICS, AND SELF-MEDICATION The jury is still out on whether the synthetic versions of THC can address the specific combination of symptoms that a PTSD sufferer is looking to relieve. The advantage of synthetics is obvious: a reliable chemical composition in a legal, prescription-grade pill or oral spray. The other components of the plant, most notably CBD, are already legally available in many countries; the US, however, still considers it a controlled substance (despite its lack of psychoactive properties). Medical Marijuana is grown specifically for medical, not recreational, use. The levels of THC are low in comparison to the other cannabinoids, and therefore the effect of the ‘high’ is mitigated. Since this is generally the opposite of what commercially available cannabis is valued for, it is unusual to obtain low-THC marijuana in street purchasing. It is more likely to find high THCV marijuana, which can create the same effect as low-THC while still carrying the psychosis risks that go along with higher levels of THC. Cannabis grown for medical use has the advantage of being chemically analyzed for specific medical application. Self-Medication is what we may call obtaining marijuana illegally for purported ‘medicinal’ use. The difference is all in the intent. Self-medication with cannabis introduces the risk of an unknown chemical content into an already unstable (PTSD) system – but if the user has the ability to regulate themselves, using only when needed, and a connection to a very reliable source, the risks are mitigated. There is a difference between using a drug for escape and using a drug for symptom management. One can liken self-medication in this sense to a PRN (as needed) prescription for benzodiazepines (clonazepam, lorazepam, diazepam, etc.). These drugs become less effective the more frequently they are used; there is an anticipation of relief that may outweigh the actual relief provided, and this encourages regular rather than occasional use; they are difficult to self-regulate in anyone with a real need for them. Ultimately, they are temporarily treating symptoms, not the core issue. In this way, the user can be lulled into thinking they are taking the necessary cure, when they really are only ingesting a stopgap panacea. CANNABIS AND PTSD: WHERE THE RESEARCH IS HEADED Two new studies on cannabis and PTSD have recently been announced in the US, both funded by the State of Colorado. One, involving 76 combat veterans with PTSD, is designed to study and compare the symptom relief provided by three different strains of cannabis. It has taken four years for primary researcher Dr. Sue Sisley and her co-sponsor, MAPS (Multidisciplinary Assoc. for Psychedelic Studies), to secure federal approval for the study protocols. This 2 million dollar grant marks the first time in 28 years that MAPS has received any kind of federal funding. Unfortunately, the research is being held up by two factors. One, Dr. Sisely has been turned down by a number of universities she has approached about hosting the study, and so there is not yet a lab to use. Two, although her research cannabis has been requisitioned for quite some time, she still does not have access to it. There is hope that the research will begin in late 2015. The other will involve 150 participants and is being run by Dr. Marcel Bonn-Miller, who has made his mark on the medical community as a primary researcher of the connections between PTSD and marijuana use. This study intends to analyze real-world cannabis use and is mainly observational in nature. The subjects will be studied in pairs. Both will have PTSD from a similar source (two combat vets, two abuse survivors, and so on). One will be a regular cannabis user; the other will have never used the drug. They will be observed for a year, and conclusions may be drawn on the positive and negative effects of cannabis on PTSD symptom management. CANNABINOIDS AND THE FEAR RESPONSE Much has been made of the relationship between marijuana and hyper-arousal. Criterion E (alterations in arousal and reactivity) covers hypervigilance, exaggerated startle response, and sleep disturbance (among others)--all of which are symptoms that most sufferers commonly claim to be alleviated by cannabis use. There is a clear scientific reason for the connection between cannabis and fear. It has emerged over the last 15 years of research, and has recently become a consistent finding in human subjects: the relationship between cannabinoid receptors in the brain and the process of traumatic memory extinction. As PTSD sufferers, we know that traumatic memory is at the core of our disorder. All therapeutic modalities designed to address trauma attempt to heal the repetitive action of traumatic memory recovery and get to a place of traumatic memory extinction - meaning, the memory stops inciting the fear response and becomes merely passive. Medications prescribed for PTSD all have one thing in common; they purport to block this 'fear response' inside the brain itself. However, these medications are doing this as a secondary action. No one intended their primary use to be in blocking traumatic memory recovery. And so, they are inconsistent at best. As mentioned earlier, there are two known cannabinoid receptors in the human body--CB1 and CB2. Receptors exist on the surface of cells and they process specific chemicals. The CB receptors process THC, CBD, CBN, etc. (all the chemicals contained within cannabis), as well as the endocannabinoids that the human body generates as part of regular function. CB1 receptors are located on brain cells, mainly concentrated in the areas that deal with memory, pain, and motor control. THC has an especially strong effect on the CB1 receptor, prompting it into over-activity and essentially flooding the brain cells it affects. It is exactly this flooding which, if managed precisely, may prove to be the mechanism by which traumatic memory is "erased." Right now the research is focused on the administering of single-dose THC to test fear extinction in human recall: participants are 'taught' a fear (generally a form of induced pain), then administered THC, and then prompted with the fear element in order to induce the memory of the fear. The preliminary findings indicate that those receiving the THC experienced complete fear extinction in their memory. Those receiving a placebo had an unchanged fear response. If the connection between CB1 receptors, traumatic memory, and the fear response can be fully mapped, it is very likely that science will not only have a profoundly deeper understanding of the impact of trauma on the brain. It will also have the chemical foundation for a post-trauma drug treatment that could serve to curtail the development of PTSD in future trauma survivors. The potential then becomes very strong for the development of a drug therapy that assists those already struggling with PTSD. IN CONCLUSION There is a great deal to be excited by in the future of cannabis research as it pertains to PTSD. Meanwhile, many sufferers will continue to seek symptom relief in marijuana use. It is important to be aware of the associated risks, as well as the research already done, and the studies just now being put into motion. If you are already using cannabis to manage your PTSD, be sure to ask yourself, "is this helping me with my treatment or is it covering up root issues I'm avoiding?" And if you have been considering using marijuana, be sure to avail yourself of the legal, medical option whenever possible. Don't rule out the possibility that the synthetic pills may be an option, if marijuana is illegal where you live. Ultimately, remember that no drug currently available is a treatment for PTSD - though continued research into cannabis, cannabinoids, and the brain will surely reveal important new developments that will change the treatment and management landscape for all PTSD sufferers, both now and in the future. **note: Arizona was mistakenly listed as a state where recreational marijuana has been legalized. Apologies for the error.