Cannabinoids such as Δ9-tetrahydrocannabinol (THC) and cannabidiol (CBD) are some of the most studied molecules in the world. A search for THC, for example, reveals approximately 10,000 scientific publications in Pubmed. Although many of these studies are on abuse potential or basic mechanisms of how it interacts with the body, they are increasingly focused on medical applications.
Medicines that include THC or CBD (or a mixture of both) have been approved by many regulatory agencies throughout the world. Medical conditions where cannabinoid-based medicines have been approved include low appetite in AIDS patients, nausea and vomiting from cancer chemotherapy, muscle spasticity from multiple sclerosis, and certain types of treatment-resistant epilepsy.
There are many other medical conditions where there is some indication that cannabinoids could be useful. This information often comes from anecdotes and in some cases is supported by tests in animal models of diseases. However, very few have completed the level of rigorous testing in clinical trials that would be necessary for approval as a medicine.
Many new clinical trials of cannabinoids have been initiated in the last few years and there are currently over 100 trials that are active at this very moment. Although federal restrictions on clinical testing of cannabinoids in the US has slowed research, many other countries have made important contributions. Results from these studies will help us understand which specific conditions have the best therapeutic potential.
Below, I will highlight some of the medical conditions where there are ongoing clinical trials of cannabinoid-based medicines. Although this is not a comprehensive list, I have chosen areas where there are multiple ongoing trials or conditions for which a large number of people use cannabis. However, it is important to remember that most of these studies are small and many more years of testing will be required to confirm their effects.
1. Chronic Pain
Chronic pain is one of the most prevalent medical conditions in the world. One recent study estimated that 20% of US adults suffer from chronic pain. Surveys show that it is also one of the most common reasons for use of medical cannabis.
Several large clinical trials of cannabinoids and chronic pain have already been completed, but some results have been conflicting and there is still much that we don't understand. Clinical testing is still ongoing, with close to 20 ongoing trials of cannabinoids in different types of chronic pain. These include studies of cancer pain, musculoskeletal pain, neuropathic pain, and pain associated with specific conditions, such as inflammatory bowel disease and Parkinson's disease.
With so many ongoing studies, it is hard to pick a few to highlight. However, one area that I find exciting is the interaction between cannabinoids and opioids. Anecdotes describe that the addition of cannabinoids (THC and/or CBD) to a patient's pain medication regimen resulted in better pain control, even while allowing them to significantly reduce their opioid dose and improve daily functioning. This "opioid-sparing effect" is supported by studies in animals, but we still need additional data from clinical studies.
One clinical study being carried out by the New York State Psychiatric Institute is assessing the analgesic effects of an opioid called oxycodone when combined with vaporized cannabis of varying THC:CBD ratios. This study is using experimentally-induced pain in healthy volunteers. Although this approach has some advantages, results will still need to be confirmed in pain patients. This study started in April of 2019 and is scheduled to be completed in 2021.
CBD is often promoted as an anti-anxiety agent. There is support for this from animal models and clinical trials, but we are still missing some key pieces of information. Single doses of CBD did decrease acute anxiety in clinical studies, but only at a dose of several hundred milligrams, which is well above the dose recommended by most products.
How can we reconcile this requirement for a high dose with the fact that most people take daily doses that are only in the tens of milligrams? Is the anti-anxiety effect at lower doses only a placebo effect? Or can lower doses actually be effective when given on a daily basis? Until now, there have been no clinical studies that have examined daily dosing for anxiety to answer these questions.
Two recently initiated clinical trials are going to provide results that will fill in this gap in our knowledge. One of these clinical trials is being carried out at McLean Psychiatric Hospital in Massachusetts. This study is testing a daily dose of 30 mg CBD as a sublingual tincture for 4 weeks in subjects with anxiety. There is a preliminary open-label phase where subjects will know that they are receiving CBD. This phase started in August 2018 and is scheduled to be completed in 2019. After this phase is complete, a second phase may be initiated that will be double-blinded and placebo-controlled.
The use of cannabinoids to treat cancer has been studied very little in humans. There is evidence from laboratory studies that they have anti-cancer activity against some tumor types. However, the results of these tumor models often do not translate to humans. Furthermore, there is a lot of information that can simply only be gained from human studies. Although some websites promote cannabinoids as a "cure" for cancer, there is currently little scientific evidence from clinical studies to back up these broad claims.
One specific tumor type in which we have seen anti-cancer activity of cannabinoids in human studies is glioblastoma (also called glioblastoma multiforme or GBM). This disease has an extremely poor prognosis, with only about 10% of patients living 5 years or more after diagnosis. Little success has been seen with recent experimental treatments, leaving patients desperate for new options.
THC and CBD have shown anti-tumor activity against glioblastoma in animal models. In fact, these cannabinoids were able to work synergistically with temozolomide, which is a chemotherapy agent commonly used for glioblastoma. This led GW Pharma to test a THC:CBD combination product in a clinical trial of glioblastoma, with promising results (see the press release).
Now a new clinical trial is being initiated by Grupo Español de Investigación en Neurooncología (Spanish Group for Neuro-oncology). This study will enroll 30 patients with newly diagnosed GBM and test how well they tolerate the combination of standard of care treatment (temozolomide and radiotherapy) and TN-TC11G, a product containing THC and CBD in a 1:1 ratio. This study was initiated in March 2019 and is scheduled to be completed in 2020. Although this trial will be relatively small and focused more on safety, it could be a step towards cannabinoids being an important new treatment advance in this disease.
Post-traumatic stress disorder (PTSD) is a disabling mental health condition characterized by persistent anxiety symptoms after experiencing a trauma. Several studies have examined the effects of cannabinoids in patients with PTSD, but these can only be considered preliminary due to small size or weak study design. Despite the current lack of strong evidence, surveys show that many PTSD patients have turned to cannabis to manage symptoms.
Cannabinoids may be used merely to manage symptoms (for example, improve sleep), but they also hold the potential to improve the course of the disease through facilitating something called "fear extinction". A fear memory can be formed after a traumatic event and is what underlies PTSD. The impact of fear memories normally fades with time due to fear extinction. But this process is often impaired in PTSD patients, leading to maintenance of fear memories.
I found 7 ongoing clinical trials that are testing cannabinoids in PTSD patients, and several of these focus specifically on fear extinction. One example is a clinical study being performed by Wayne State University in Michigan, which is assessing the effects of THC. This study will initially form a fear memory in PTSD patients by associating an image with an aversive stimulus such as a loud noise. The next day, patients will receive either oral THC or placebo prior to viewing the image again. At later visits, the extent of fear extinction will be assessed by showing the subjects the image and measuring anxiety levels, physiologic responses, and brain activity. This study started in June 2017 and is scheduled to be completed at the end of 2019.
5. Drug Dependence
Drug dependence is a serious problem. This has never been more obvious than the past few years, when opioid overdose deaths in the US have skyrocketed. But despite the damage caused by a variety of addictive drugs, including alcohol and nicotine, effective treatment options have always been in short supply.
CBD may represent a new tool to treat drug dependence. Your brain's reward system becomes dysregulated after developing drug dependence, and this cannabinoid may reverse some of these changes. CBD can interact with the endocannabinoid system and several neurotransmitter systems that are important for the regulation of reward and drug seeking.
CBD reduces drug-seeking behavior in animals for a variety of different addictive drugs. Now the ability of CBD to combat addiction is being tested in several clinical trials, including studies in patients with alcohol dependence, cocaine dependence, and opioid dependence.
For example, one clinical study of opioid dependence is being carried out by University of California, Los Angeles. This study will assess opioid dependent patients who are undergoing residential treatment with the use of buprenorphine and naloxone. These patients will be randomized to receive placebo or an oral solution of CBD, at doses of either 700 or 1400 mg. Over 4 weeks of treatment, patients will be assessed on their craving for opioids and several other symptoms of drug dependence. This study is scheduled to start in June 2019 and is scheduled to be completed in 2021.
Promising results in these trials could propel CBD to be an important new treatment option in drug dependence. There is an irony in this - the War on Drugs suppressed medical cannabinoid research in the US, but it is this very research that may end up helping patients suffering from drug dependence.
There are many exciting clinical trials of cannabinoids that are currently ongoing. This list only contains a few examples, but there are many more medical conditions for which cannabinoids are being tested. I am eagerly awaiting the results of these trials and many others. These results will help us better understand how cannabinoids could be used to help patients with a variety of medical conditions.