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NIDA

Researching the Potential Medical Benefits and Risks of Marijuana

July 13, 2016
presented by Susan R.B. Weiss, Ph.D. - Director, Division of Extramural Research
Senate Judiciary Committee, Subcommittee on Crime and Terrorism
Dr Susan Weiss testifying before the Senate Dr. Susan Weiss testifying on "Researching the Potential Medical Benefits and Risks of Marijuana" before the Subcommittee on Crime and Terrorism. Watch the video on the Senate web site.

Chairman Graham, Ranking Member Whitehouse, and Members of the Senate Judiciary Subcommittee on Crime and Terrorism, thank you for inviting the National Institute on Drug Abuse (NIDA), a component of the National Institutes of Health (NIH), to participate in this hearing to review the state of the science on the therapeutic potential of marijuana and its constituent compounds and to discuss ways of facilitating more research in this area.  

Background

While marijuana use remains illegal at the federal level, to date 25 States and Washington, D.C. have passed laws allowing marijuana to be used for a variety of medical conditions.  An additional 16 States have passed laws that specifically permit the medical use of cannabidiol (CBD), one of approximately 100 cannabinoid chemicals found in the marijuana plant.  There is a growing body of research suggesting the potential therapeutic value of cannabinoids in numerous health conditions including pain, nausea, epilepsy, obesity, wasting disease, addiction, autoimmune disorders, and other conditions.  However, in general, adequate and well-controlled studies are lacking, which means that patients across the country are using marijuana strains and extracts that have not undergone rigorous clinical trials, are not regulated for consistency or quality, and are used for medical conditions with an insufficient evidence base supporting their effectiveness.

NIH believes that FDA’s drug review and approval process represents the best way to ensure that new medicines, including those derived from marijuana, are appropriately evaluated for safety and effectiveness.  The Food and Drug Administration (FDA) has approved three medications, Marinol (dronabinol), Cesamet (nabilone), and Syndros (oral drabinol solution), for severe nausea and wasting in patients with HIV and cancer.  These medications contain synthetically-derived cannabinoids. Dronabinol is identical in chemical structure to delta-9-tetrahydrocannabinol (THC), the main active ingredient found in the marijuana plant; nabilone is similar in structure to THC.

With Americans across the country consuming marijuana for health related conditions, there is a pressing need for more research in this area.  The progress of therapeutics development and clinical trials has been slow, in part due to the increased time, costs, and administrative efforts associated with the regulatory framework for conducting research on these and other Schedule I compounds.  NIH is committed to working with Congress and our federal partners to facilitate more research on the therapeutic potential of marijuana and cannabinoids and to reduce barriers to research.

Therapeutic Potential of Marijuana and Constituent Cannabinoids

Cannabinoids exert their effect mainly by interacting with two types of receptors: CB1 and CB2 receptors.  CB1 receptors are located mainly on neurons and glial cells in the brain and in several other organs in the body.  CB2 receptors are found mainly on immune cells, and are less common in the brain than CB1 receptors.1 The majority of the research on the therapeutic potential of marijuana has focused on two cannabinoids: THC and CBD.  The euphoric effects of marijuana are caused by THC through activation of CB1 receptors.  CBD has a very low affinity for these receptors (100-fold less than THC), and when it binds it produces little to no effect.  Consequently CBD does not appear to produce euphoria or intoxication.  CBD acts on other brain signaling systems (e.g., serotonin receptors), and it is these actions that are thought to be important to its therapeutic effects.2

Beyond the two THC-based medications already approved by the FDA, at least 79 clinical trials have been published exploring the therapeutic effects of marijuana or its constituent cannabinoids.3  These studies have suggested potentially valuable therapeutic effects of marijuana or its components in several areas.

Pain/Spasticity: Nabiximols (trade name Sativex), which contains THC and CBD in equal proportions, has been approved throughout most of Europe and in a number of other countries for the treatment of spasticity and pain associated with multiple sclerosis (MS).  Multiple recent studies have confirmed that nabiximols (Sativex) reduced the severity of spasticity in MS patients,4 including two studies recently presented at the European Committee for Treatment and Research in Multiple Sclerosis annual meeting.5 Sativex has not been approved in the United States, where it is being developed for the treatment of refractory pain in cancer patients;  two recent Phase 3 clinical trials did not achieve the expected clinical endpoint.6 

Two recent reviews, one in the Journal of the American Medical Association3 and another by the American Academy of Neurology7 concluded that there is moderate evidence to suggest that some cannabinoids, including nabiximols, may be beneficial for the treatment of chronic neuropathic or cancer pain and spasticity due to MS, and strong evidence for the efficacy of oral cannabis extract for spasticity and pain associated with MS.4,8 In contrast, they also concluded that there was insufficient evidence for the use of cannabinoids in the treatment of involuntary movement disorders such as Huntington’s disease or Tourette’s syndrome. 

Pediatric Epilepsy:  A number of case studies and anecdotal reports, as well as a few small randomized clinical trials (RCTs), have also suggested that CBD may reduce seizures in children with treatment-resistant epilepsy.  GW Pharmaceuticals is currently conducting two placebo-controlled, multicenter Phase III studies examining Epidiolex, a formulation of CBD, for both Dravet syndrome and Lennox-Gastaut syndrome, severe forms of pediatric epilepsy.  According to company press releases in March and June 2016, initial results from the first Phase 3 trials of Epidiolex were positive.  The first trial showed a median reduction in monthly convulsive seizures of 39 percent among patients with Dravet syndrome who took Epidiolex compared with 13 percent for placebo9. The second trial showed a median reduction in monthly drop seizures of 44 percent among patients with Lennox-Gastaut syndrome who took Epidiolex compared with 22 percent for placebo.9  Insys Therapeutics has developed synthetic CBD and Phase 2/3 studies are underway.10 In May 2016, they reported successful completion of a Phase 1/2 safety and pharmacokinetic (PK) study in pediatric subjects with treatment-resistant epilepsy.11

Post-traumatic Stress Disorder:  Human laboratory studies have also suggested that THC administration may help facilitate fear extinction in healthy subjects which could have implications for treating patients with post-traumatic stress disorder (PTSD).12 RCTs are currently ongoing that will examine the therapeutic value of smoked cannabis and dronabinol for patients with PTSD.

Other Potential Indications (Pending Future Research):  There is some preliminary evidence from human trials for a potential therapeutic benefits of cannabinoids for the conditions listed below.  Rigorous RCTs are needed because initial promising results are often not confirmed by subsequent more rigorous testing:

  1. THC for tics in Tourette syndrome13
  2. THC or THC/CBD for sleep disorders14
  3. Both CBD and THC in the treatment of substance use disorders including nicotine, cannabis, and opioid addiction15,16
  4. CBD for anxiety in individuals with social phobia17
  5. CBD for psychosis in patients with schizophrenia18

Beyond these indications, pre-clinical research (including cell culture and animal models) has suggested that marijuana, THC, and/or CBD may have a range of therapeutically useful effects including analgesic, anti-seizure, antioxidant, neuroprotective, anti-inflammatory, anti-tumor, anti-psychotic, and anti-anxiety properties.1  More research is needed to follow up on these findings to determine if they will translate to therapeutic benefits for human health.

Current NIH Research on Marijuana and Cannabinoids

NIH supports a broad portfolio of research on cannabinoids and the endocannabinoid system.  This research portfolio includes some studies utilizing the whole marijuana plant, however most studies focus on individual cannabinoid compounds or other strategies to manipulate the function of the endogenous cannabinoid system.  The marijuana plant itself is not considered an ideal medication candidate because:

  1. It is an unpurified plant containing numerous chemicals that have not been fully characterized;
  2. The variability of active components makes it difficult to reproduce a consistent dose;
  3. It is often consumed by smoking, potentially contributing to adverse effects on lung health;
  4. Its cognitive- and motor-impairing effects may limit its utility.

In FY 2015, NIH supported 281 projects totaling over $111 million on cannabinoid research.  Within this investment, 49 projects ($21 million) examined the therapeutic properties of cannabinoids, including 15 projects ($9 million) focused on CBD.  Cannabinoid research is supported broadly across 17 NIH Institutes and Centers (ICs), with each IC supporting research specifically focused on the impact of cannabinoids on health conditions within their scientific mission.

Since 2011, there have been 139 clinical trials listed on clinicaltrials.gov studying the therapeutic potential of marijuana, CBD, and/or THC for a range of conditions including 10 NIH-supported trials for:

  1. Cannabis use disorder;
  2. Pain;
  3. Sickle cell anemia;
  4. Spinal cord injury;
  5. HIV related symptoms;
  6. Irritable bowel syndrome.

In March 2016, NIH convened a meeting entitled “Marijuana and Cannabinoids: A Neuroscience Research Summit” which focused on the neurological and psychiatric effects of marijuana, other cannabinoids, and the endocannabinoid system.  The goal of the Summit was to ensure evidence-based information is available to inform practice and policy, particularly important at this time given the rapidly shifting landscape regarding the recreational and medicinal use of marijuana.  More than 2,000 researchers, policy makers, clinicians, and members of the public attended the Summit, either in person or through the videocast. A summary of the summit can be found at http://apps1.seiservices.com/nih/mj/2016/Documents/BriefMJSummitMeetingSummary.pdf

Facilitating Research on Marijuana and Cannabinoids

The current state of the research on marijuana and its constituent cannabinoids suggests the potential for therapeutic value for a number of conditions; however, more evidence is needed before marijuana or cannabinoid products (beyond those already FDA-approved) are ready for medical use.  Promising preclinical findings do not always prove to be clinically relevant, and even fewer lead to new treatments.19  Moreover, clinical studies of sufficient quality to meet FDA standards for drug approval are currently lacking for most conditions.  Among the factors that impact this research are the specific statutory requirements and treaty obligations that govern research on marijuana. NIH is working closely with the Office of National Drug Control Policy (ONDCP), the Drug Enforcement Administration (DEA), and FDA to explore ways to streamline these processes to facilitate research. Outlined below are some of the barriers or perceived barriers that we are attempting to overcome in this regard.

Under the Single Convention on Narcotic Drugs (1961), the United States is subject to several obligations related to the regulation of marijuana cultivation for research.20  In addition, under the Controlled Substances Act (CSA), marijuana and its constituent compounds are classified as Schedule I controlled substances – defined as having high potential for abuse and no currently accepted medical use, and no accepted safety for use under medical supervision.21  As a result of these treaty obligations and marijuana’s status under the CSA, (DEA) with input from the Department of Health and Human Services regulates marijuana research and the cultivation of marijuana for research purposes through licensing requirements and by establishing annual aggregate production quotas. While research on marijuana and its constituent compounds is possible, there remains a number of barriers, described below, for doing this research22.

The registration process:  Researchers have indicated that this process creates administrative burdens that can act as disincentives to conducting research. To help ease this burden NIDA and the DEA have been communicating directly, with the specific aim of reducing the time to it takes for researchers to get their Schedule I registration.

The Evaluation of constituent compounds: Per the CSA, all of the cannabinoids in marijuana are considered Schedule I compounds.  Currently, evidence suggests that CBD does not have abuse liability.  FDA has indicated that a human abuse liability study will be necessary to make a final determination on the abuse liability of CBD, which would be factored into the scheduling recommendation.  NIH and FDA have committed to conducting this study and are working out the final details now.

Further, starting on December 16, 2015, the DEA Deputy Assistant Administrator, Office of Diversion Control mailed waiver letters to advise clinical researchers handling CBD under a FDA-approved investigational new drug application (IND) that DEA will accept applications from researchers who are currently registered to conduct clinical research with material that contains CBD, within the ranges specified (contain at least 98% of CBD), for a waiver of certain regulatory requirements that apply when the registrant seeks to make certain modifications to the research protocol.  Our DEA colleagues tell us that as of July 12, 2016, DEA has received and granted all requested (42) waivers to researchers. DEA has taken approximately 11 days to grant these requests once received.

Single source of marijuana for research purposes:  Currently, there is one registration for marijuana cultivation in the US, the University of Mississippi, which, through a contract with NIDA, supports the cultivation and distribution of research grade marijuana for the country.  While the NIDA supply of marijuana has diversified to include different strains with varying concentrations of CBD and other cannabinoids of interest to researchers, it is both costly and time consuming to grow, isolate, and/or refine new products that scientists would like to study. NIDA on July 7, 2016 issued a request for information that is seeking feedback on which specific strains and products are currently of greatest interest to researchers.

Path from use of NIDA-supplied marijuana to market:  The University of Mississippi, under the contract with NIDA, currently produces a limited number of marijuana extracts for researchers to use in drug development.  Drug developers would need to transition from using NIDA-supplied marijuana products to other sources before FDA approval and market. It may be challenging for a pharmaceutical company to demonstrate equivalency between the marijuana used in the clinical trials and the drug product that will be marketed. While FDA has provided guidance on how this should occur27, the process requires additional time and resources of the developer.

The DEA has been working with NIDA, ONDCP, and the FDA to identify strategies to make marijuana available from other sources, which could both speed the pace of research and afford individual developers and researchers more options in formulating a marijuana-derived investigational products for eventual marketing.

Addressing These Barriers: Multiple agencies (NIH, ONDCP, DEA, and FDA) are working together to find ways to streamline the process to facilitate research while meeting international and legislative obligations under the Single Convention on Narcotic Drugs and the Controlled Substances Act. In addition to actions taken by the Department of Health and Humans Services to eliminate the Public Health Services (PHS) committee review for non-federally funded marijuana research,23 the DEA recently streamlined the administrative process for CBD research to allow researchers to obtain a waiver of the requirement for review of changes to an approved protocol in their DEA research registrations,24 and is attempting to address the marijuana diversity and product development concern by licensing additional manufacturers.

Conclusion

We appreciate the concerns of the Committee and share a mutual interest in supporting the development of safe and effective treatments to improve the health of our citizens while maintaining a commitment to rigorous clinical research.  Rigorously conducted randomized trials are needed to confirm preliminary evidence suggesting the potential therapeutic value of cannabinoids for a variety of conditions and symptoms.  Additional clinical and basic research is needed to support the development of new medications.  NIH will continue to support research towards this end.

Questions for the Record from Senator Richard Blumenthal

Question #1: How should lawmakers think about future research? 

I was a strong supporter of provisions in the 2012 Food and Drug Administration Safety and Innovation Act that sought to address the harms caused by synthetic marijuana. And just a few weeks ago we had another hearing on the synthetic drug crisis because scheduling law is still struggling to keep up with the new and dangerous compounds that are emerging and wreaking havoc on families and communities.

But on the heels of some promising research, the Surgeon General, Vivek Murthy, has come out and said that marijuana potentially has medical benefits, and that we need to do more research. 

Dr. Weiss, in your testimony you indicated that current evidence does not support the conclusion that certain components of marijuana, such as the CBD cannabinoid, have the potential for abuse. You also noted evidence suggesting potential therapeutic benefits from several components of marijuana. But primarily, it seems that you underscored the need for further research.  

What steps should lawmakers take to make sure we are adequately researching the potential benefits and risks of medical marijuana? How can we, as lawmakers, along with the NIDA, balance the need to break barriers to research with the need to keep certain dangerous compounds from leading to abuse and fatalities? 

Response: As discussed in our testimony, NIDA has been working closely with the Office of National Drug Control Policy (ONDCP), the Drug Enforcement Administration (DEA), and the Food and Drug Administration (FDA) to identify ways of facilitating more research on marijuana and its constituent cannabinoids while maintaining compliance with the international treaties and the Controlled Substances Act (CSA). There are a number of factors that have contributed to the slow pace of research on marijuana and its constituent compounds. 

  • The Schedule I registration process and required protocol review:  NIDA has heard from some researchers that this process creates administrative burdens that can act as disincentives to conducting research.  To help ease this burden NIDA and the DEA have been communicating directly, with the specific aim of reducing the time to it takes for researchers to get their Schedule I registration. Schedule I status of cannabidiol (CBD): Currently, evidence suggests that CBD does not have abuse liability.  FDA has indicated that a human abuse liability study will be necessary to make a final determination on the abuse liability of CBD, which would be factored into the scheduling recommendation. NIH and FDA are in the process of finalizing the details regarding the methodology and budget needed to conduct this study.
  • Single source of marijuana for research purposes:  As noted in our testimony, there is currently only one DEA-registered source of marijuana for research in the country. However, in August 2016 DEA announced a new policy that is designed to increase the number of entities registered under the Controlled Substances Act (CSA) to grow (manufacture) marijuana to supply legitimate researchers in the U.S.
  • Clarifying the path from use of NIDA-supplied marijuana to market:  As discussed in our testimony, pharmaceutical companies would need to transition from using NIDA-supplied marijuana products to other sources before FDA approval and marketing. Additional studies would likely be needed, per FDA requirements, for post-approval changes in product manufacturing, to demonstrate equivalency between the marijuana used in the clinical trials and the drug product that will be marketed. Further, the efforts by DEA to make marijuana available from additional sources, discussed above, could help to address this issue.
  • Limited funding: While the percentage of grant proposals for cannabinoid research submitted to NIH that receive funding is equivalent to other categories of research, funding availability does impact the pace of research.

Question #2: What potential role is there for medical marijuana in combatting the opioid crisis? 

I’m sure you’re aware of the many conversations that we’ve had in this body on the horrible opioid crisis that is plaguing many states, including my home state of Connecticut. In 2012, Connecticut saw 86 heroin overdose deaths, and one overdose of heroin and fentanyl. In 2015, Connecticut saw 415 heroin deaths, and 107 fentanyl deaths. Today we have been debating the Comprehensive Addiction and Recovery Act, which I believe is an important step forward in addressing this public health emergency even though I believe it has significant flaws. As you well know, we need all of the information and help we can get to combat the scourge of opioid abuse.  

In your testimony, you mentioned that there is some evidence that cannabinoids may help treat substance use disorders like opioid addiction. There is also evidence indicating that states with medical marijuana programs are linked to decreases in opioid abuse and mortality. 

a. Bearing in mind that further research is needed, what potential role could cannabinoids play in helping treat opioid abuse? 

Response: One of the pillars of the Secretary’s Opioid Initiative is to improve opioid prescribing practices to reduce the use of opioid pain relievers and prevent and reduce prescription opioid misuse1. NIH is actively involved in this initiative and development of non-opioid treatments for pain is a high priority research area. There are numerous studies that have suggested a potential role for cannabinoids in mediating and potentially treating pain. For example: 

  • Activating cannabinoid receptors in pain processing regions, from peripheral nerves, to the spinal cord and the pain-perception systems of the brain has been shown to suppress pain2.
  • Drugs that selectively activate the CB2 cannabinoid receptor show promise in relieving pain without unwanted psychotropic side effects3.
  • A recent meta-analysis identified moderate-quality evidence to support the use of cannabinoids for chronic pain4, and a recent review by the American Academy of Neurology5 concluded that there is strong evidence for the efficacy of oral cannabis extract for spasticity and pain associated with multiple sclerosis (MS) and moderate evidence for the efficacy of THC and nabiximols for pain associated with MS6,7.
  • Cannabidiol (CBD), a component of marijuana that all available evidence suggests is non-psychotropic, also shows therapeutic potential for pain8.
  • In one study of vaporized cannabis, significant improvement in pain was present at low doses that had minimal psychoactive effects9.
  • Initial studies have suggested that cannabinoids may enhance the pain relieving properties of opioids, reducing the dose of opioids needed for pain relief, which could reduce adverse outcomes including overdoses 10,11

Note that the majority of these studies refer to the cannabinoid components of marijuana and not to smoked marijuana. The marijuana plant itself is not considered an ideal medication candidate because: 

  • It is an unpurified plant containing numerous chemicals that have not been fully characterized.
  • The variability of active components makes it difficult to reproduce a consistent dose.
  • It is often consumed by smoking, potentially contributing to adverse effects on lung health.
  • Its cognitive- and motor-impairing effects may limit its utility.

Pain is a condition for which a large proportion of patients in medical marijuana states seek treatment12,13 and, as noted in your question, medical marijuana laws have been associated with changes in opioid prescribing and outcomes. Two recent studies found an improvement in adverse opioid outcomes associated with the legalization of marijuana for medicinal use. The first found that the implementation of medical marijuana laws was associated with a slowing of the increase in opioid overdose deaths, an effect that strengthened in each year following the implementation of legislation15. The second showed that access to medical marijuana dispensaries is associated with a reduction in opioid prescribing, self-report of nonmedical prescription opioid use, treatment admissions for prescription opioid use disorders, and in prescription opioid overdose deaths16.  Though these studies are not definitive, and marijuana use can be associated with its own harms17; one recent study found that increased availability of medical marijuana dispensaries was associated with increased risk for cannabis use disorders18. However, these studies raise the possibility that marijuana-derived products may have a role as alternative or adjunct treatments for pain with potential utility for reducing the use of opioids needed to control pain. More research is needed to investigate this possibility.  

Cannabinoids are also being studied for their potential to treat substance use disorders, including opioid use disorder. While the evidence base is less robust than that supporting the efficacy of cannabinoids for pain treatment, preclinical studies have suggested that CBD reduces the rewarding properties of opioids, reduces relapse-like behaviors, and has the potential to mitigate symptoms of opioid withdrawal19.  Pilot data in human subjects show a reduction in heroin craving after treatment with cannabidiol20. More research is needed to determine if these preliminary findings can translate into meaningful clinical outcomes. 

b. What steps do you believe need to be taken in order to fully realize the benefits of cannabinoid research in combatting the opioid crisis? 

Response: More research is needed to follow up on these findings to determine if they will translate to therapeutic benefits for human health. Preclinical and early clinical findings frequently fail to translate to safe and effective therapeutics21, so the true potential of cannabinoids for the treatment of pain and opioid use disorders cannot be determined without large-scale, randomized controlled trials (RCTs) . As noted in our testimony, nabiximols (trade name Sativex), which contains THC and CBD in equal proportions, has been approved throughout most of Europe and in a number of other countries for the treatment of spasticity and pain associated with MS, however, it has not been approved in the United States, and results from two Phase 3 clinical trials for severe refractory cancer pain were not encouraging22. In this case, as in others, it is possible that this medication may be effective for other types of pain or for less severe pain, however, more clinical trials are needed to test these possibilities and potentially develop therapeutics that can pass the rigorous standards required for FDA drug approval. 

In addition to our research portfolio on the roles of the cannabinoid and opioid systems in pain, NIDA has funded numerous studies that will provide data relating to medical marijuana and opioids, specifically: 

  • Effects of access to medical marijuana on substance use, including nonmedical use of prescription opioids (DA031816-05, DA039293-01A1, DA037341-02, DA032693-04)
  • Mental and physical functioning of a cohort of pain patients seeking medical marijuana treatment (DA033397-03)
  • The impact of medical marijuana policies on health outcomes (DA034067-03)

Question #3: What role might medical marijuana play in treating post-traumatic stress? 

As ranking member on the Senate Committee on Veterans Affairs, I am keenly aware of the mental toll that war has taken on our service members, especially through posttraumatic stress. Due to its devastating effects, especially on people who have so bravely served our country, I believe we need to look at every possible method of treatment. In your testimony, you mentioned that there is some evidence that cannabinoids may help treat posttraumatic stress. 

a. Can you talk more about what research has suggested about the potential for cannabinoids to help treat PTSD, especially combat-related PTSD? 

Response: Both preclinical and human laboratory studies have suggested that cannabinoids may have therapeutic potential for the treatment of PTSD.  However, it should be noted that the marijuana plant contains over 100 cannabinoids and, as noted above, at different doses cannabinoids can have opposite effects. Careful research is needed to determine whether any of the components of marijuana have therapeutic potential for the treatment of PTSD.   

Studies have shown that PTSD is associated with several changes in the body’s endogenous cannabinoid – or endocannabinoid – system including: 

  • increased cannabinoid receptor 1 (CB1) receptor availability in the brain23;
  • changes in concentrations of naturally occurring or endogenous cannabinoids24,25;
  • genetic variations in an enzyme that degrades endogenous cannabinoids (FAAH)26; and

CB1 receptors are present in areas of the brain involved in the processing of anxiety and fear, and can affect how threats are perceived. Studies in animal models support the critical role of CB1 receptors, and the broader endocannabinoid system, in appropriately matching level of anxiety to the danger posed by a perceived threats27,28 and for appropriate extinction of aversive memories29,30; functions that are disrupted in patients with PTSD. Preclinical research has shown that: 

  • THC reduces anxiety in some animal models of PTSD; importantly, efficacy was dependent on dose with low doses reducing anxiety and high doses increasing anxiety31,32.
  • [7]WIN 55,212-2, a cannabinoid that activates CB1 receptors33,34 and cannabidiol (CBD)35 also show dose-dependent efficacy for enhancing fear extinction – the process where a cue that once elicited fear (such as loud noises eliciting fear associated with combat) gradually stops being associated with fear.

As noted in our testimony, one study found that THC administration may help facilitate fear extinction in healthy subjects which could have implications for treating patients with PTSD36. Several human studies have examined cannabinoids for the treatment of PTSD.  Most of these studies have been small, non-randomized, lacking sufficient control groups and power, and they have produced mixed results, of the positive findings: 

  • A study using Nabilone, a synthetic cannabinoid similar in structure to THC, to treat insomnia, nightmares, and pain in patients presenting with serious mental illness successfully reduced many PTSD symptoms including pain37.
  • Human studies utilizing oral Dronabinol, a synthetic cannabinoid identical to THC, to aid fear extinction showed some improvement in reactivity to fear related cues; however, fear extinction was not improved38.

These and other findings suggest that the endocannabinoid system plays a role in the brain functions that are impaired in patients with PTSD and that this system is a potential therapeutic target for these patients. There is growing evidence that people, including veterans, are using marijuana to cope with PTSD symptoms, with usage tending to increase as the severity of PTSD symptom increases39(p),40–43 ; however, studies have shown mixed results on the efficacy of marijuana for reducing PTSD symptoms and an increasing number of veterans with PTSD are being diagnosed with cannabis use disorder44. Also, note that these studies refer to the cannabinoid components of marijuana and not to smoked marijuana. The marijuana plant itself is not considered an ideal medication candidate because: 

  • It is an unpurified plant containing numerous chemicals that have not been fully characterized.
  • The variability of active components makes it difficult to reproduce a consistent dose.
  • It is often consumed by smoking, potentially contributing to adverse effects on lung health.
  • Its cognitive- and motor-impairing effects may limit its utility.

Further research is needed to determine which cannabinoids, at what doses, may be safe and effective for the treatment of PTSD.  

b. What steps do you believe need to be taken in order to fully realize the benefits of cannabinoid research in helping our veterans recover from invisible wounds of war? 

Response: As discussed above, additional research is needed to determine which cannabinoids, at what doses, may be safe and effective for the treatment of PTSD. Preclinical and early clinical findings frequently fail to translate to safe and effective therapeutics, so the true potential of cannabinoids for the treatment of PTSD cannot be determined without large-scale, randomized controlled trials (RCTs). In addition, comparative effectiveness studies will be needed to determine how marijuana and/or cannabinoids compare to conventional behavioral and pharmacotherapies currently used to treat PTSD (e.g. prazosin, selective serotonin reuptake inhibitors, second-generation antipsychotics)36.

References:

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  8. Ward SJ, McAllister SD, Kawamura R, Murase R, Neelakantan H, Walker EA. Cannabidiol inhibits paclitaxel-induced neuropathic pain through 5-HT(1A) receptors without diminishing nervous system function or chemotherapy efficacy. Br J Pharmacol. 2014;171(3):636-645. doi:10.1111/bph.12439.
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Testimony to Congress

June 30, 2017

July 29, 2016

July 13, 2016

January 27, 2016

July 27, 2015

June 24, 2015

May 01, 2015

August 12, 2014

June 20, 2014

May 14, 2014

April 29, 2014

April 02, 2014

September 25, 2013

March 20, 2012

May 11, 2011

September 22, 2010

June 23, 2010

April 21, 2010

May 21, 2009

April 29, 2009

March 12, 2008

March 05, 2008

February 12, 2008

March 01, 2007

November 14, 2006

July 26, 2006

June 28, 2006

March 16, 2006

February 08, 2006