with David Bearman MD, and Janice Newell Bissex, MS, RDN, FAND

As of early 2021, medical cannabis is legal in 34 US states, with the leading use of medical marijuana being pain relief – especially chronic pain.¹˒² Many people report preferring cannabis to other drugs because it has a low side effect profile and is generally regarded as nonaddictive. However, researchers at the University of Michigan are questioning these widely accepted notions.

In reporting the results of longitudinal survey studies completed over the course of 2 years, a research team led by Lara N. Coughlin ultimately proposed that medicinal cannabis containing THC (as compared to hemp or CBD) use may indeed come with withdrawal symptoms upon cessation. The researchers looked not only at the existence of withdrawal symptoms but also the stability of marijuana withdrawal symptoms over 24 months.³

Medical Marijuana Users, Study Demographics

The study, published in Addiction, used detailed survey results completed by 527 patients with chronic pain seeking medicinal marijuana certification or recertification. Participants reported withdrawal symptoms using the Marijuana Withdrawal Checklist-revised at baseline and again at 12 months and 24 months. Latent class analysis (LCA) was used to examine baseline marijuana withdrawal while latent transition analysis (LTA) was used to examine longitudinal development of symptoms across the designated time points.

During baseline measurement, participants were grouped into initial withdrawal classes based on the intensity and amount of withdrawal symptoms reported: mild, moderate, orsevere. An exploratory analysis was used to determine the demographic and clinical characteristics predictive of withdrawal class.

Participants were predominantly white (82%) and evenly split by sex. Average age was 45.6 years. Data from those with cancer-related pain were excluded.

Among the limitations shared by the researchers: nicotine use was not accounted for and breakthrough pain was not controlled for; withdrawal symptoms were self-reported retroactively, and could be compounded by patients’ pain experience when recollecting events; the particular variety of cannabis product was unaccounted for; because different products have different ratios of cannabinoids, terpenes, etc, it is difficult to form a general classification of withdrawal symptoms from this study alone.

Marijuana Withdrawal Symptoms Reported

Of the three groups, below are the withdrawal symptoms reported upon stopping marijuana use:

• 41% of participants reported mild withdrawal symptoms, with the most common being marijuana cravings and sleep difficulties

• 34% of participants fell into the moderate group with the most commonly reported withdrawal symptoms being marijuana cravings, sleep difficulties, depressed mood, decreased appetitive, anxiety, restlessness, and irritability

• 25% of participants reported severe withdrawal symptoms that included cannabis cravings, anxiety, sleep difficulties, decreased appetite, restlessness, depressed mood, aggression, irritability, nausea, sweating, headache, stomach pain, strange dreams, increased anger, and shakiness.

• Of note, sweating was not reported by any group.

(More on short-term effects of medical marijuana use.)

Marijuana Withdrawal Symptoms Worsened for Some, Improved for Others

Whether or not the reported symptoms can be directly related to withdrawal from marijuana use, one focus in this study was on the stability of these symptoms and factors that were likely to influence that stability over time (ie, 24 months).

• People in the mild group at baseline were likely to stay at that level, although some did progress to the moderate group by the end of the 2-year period.

• People who began in the moderate group were more likely to see their symptoms improve and end the study in the mild group at the 2-year mark.

• People reporting severe withdrawal symptoms at baseline were more likely to be longtime or frequent users of cannabis, more likely to be younger, and more likely to have a worse mental health profile.

Marijuana “Withdrawal” Symptoms More Likely to Be Symptoms of Chronic Pain Condition

In line with the limitations noted by the research team, David Bearman MD, EVP of the American Academy of Cannabinoid Medicine and Certified Cannabinoid Medicine Specialist, believes, “It is very likely that the symptoms reported in this study are not withdrawal symptoms but the return of chronic pain and its confounders that the cannabis was being used to treat,” he told PPM. Dr. Bearman has worked in the treatment of drug addiction and prevention for five decades.

Janice Newell Bissex, MS, RDN, FAND, co-director of the Cannabinoid Medical Sciences Program at the John Patrick University School of Integrative & Functional Medicine in Indiana, agrees. “The majority of the symptoms reported in this study are the same symptoms that the cannabis is used to treat for,” she told PPM. “However, with classical withdrawal symptoms, we usually expect them to improve with time. The fact that these symptoms worsened with time (or remained the same) makes me think they were most likely symptoms of the chronic pain condition.”

(More on using medical cannabis for multiple sclerosis pain and function.)

How to Counsel Patients About Medical Marijuana Withdrawal and THC Tapering

What can be ascertained from this study and how can clinicians be mindful of potential withdrawal symptoms from medical marijuana use?

“When you use an exogenous cannabinoid (cannabis) long-term, your endogenous cannabinoids will down-regulate. When you take away the exogenous cannabinoids, it takes time for your body to regulate your endogenous cannabinoids,” explains Bissex.

While cannabis is not a hormone, its use may be compared to the way that patients need to adjust after discontinuing synthetic thyroid hormones, for example. She adds that “longtime cannabis users should be advised to take breaks in cannabis use (when THC is involved). If someone is using cannabis for pain management and wants to discontinue use, they should slowly taper their cannabis use – similar to the way you would with an antidepressant,” she explains. “Patients can also supplement with CBD, to help with some of the anxiety and sleep issues that may accompany the discontinuation of cannabis.”

The clinician, noted Bissex, should be aware that during the initial THC tapering period, patients may experience breakthrough pain, trouble sleeping, and an increase in pain-related symptoms. As is the case when any treatment is removed, the patient should be supported with alternative therapies.

Anecdotally, in their own pain practices, Bissex and Dr. Bearman both shared that they have not had patients who reported withdrawal symptoms from stopping medical marijuana use.

New Jersey residents undergoing treatment for opioid addiction will now be allowed to use medical marijuana as part of their treatment plan, effective immediately, due to changes implemented by Governor Phil Murphy.¹ In addition, Gov. Murphy announced that starting in April 2019, the state’s Medicaid program will end its policy of requiring prior authorization for medication-assisted treatment (MAT) for opioid use disorder (OUD).

According to officials, all residential treatment facilities in New Jersey paid by Medicaid must offer MAT starting in July 2019. The state will start rolling out patients suffering from OUD to enroll in the state's medical marijuana program in conjunction with MAT. Previously, only patients suffering from chronic pain, migraine, and other conditions were eligible to enroll in the state’s medical marijuana program.

Prior Medicaid authorizations have been a barrier to some, according to Gov. Murphy in an announcement made at Cooper University Health Care, in Camden, NJ. “Removing unnecessary barriers to MAT is the right thing both for patients and providers,” Murphy said in his announcement. He added that Medicaid recipients nationally make up an estimated 40% of opioid addiction patients.

In other efforts, NJ Human Services Commissioner Carole Johnson announced that her department would train more doctors to provide MAT for opioid addiction, create new Medicaid reimbursement incentives to encourage such treatment, and establish a “Centers of Excellence” for opioid treatment at both Rutgers and Rowan Universities.

Read a commentary by Jeff Gudin, MD, on these legal changes.

Which States are Expanding Medical Marijuana Use?

New Jersey follows Pennsylvania in its actions and several other states may soon follow suit and allow OUD to be a qualifying condition as part of their respective programs; here is what a few states are doing now:

• Pennsylvania: In April 2018,2 the Pennsylvania Medical Marijuana Advisory Board recommended that medical marijuana be considered for opioid addiction therapy and opioid reduction. The state now includes OUD as a qualifying condition for medical cannabis. In July 2018, the state funded eight state universities to conduct medical marijuana research to improve understanding and awareness of opioid addiction.3

• Ohio: The state’s Medical Board has recently accepted petitions on adding qualifying conditions for doctors to recommend medical marijuana treatment, including opioid use disorder, through the end of 2018, with a decision to be made later in 2019.⁵

• Maine: In January 2016, a petition submitted to the Maine Medical Use of Marijuana Program encouraged adding opioid addiction to qualify for medical marijuana. Upon further review, the state’s Medical Marijuana Advisory Committee could not conclude that the use of medical marijuana for opioid addiction was safe and the petition was denied. Efforts to add OUD to the list of qualifying conditions are continuing in the state’s legislature.⁶

• New Mexico: In 2017, New Mexico included the addition of OUD to the list of qualifying conditions for medical marijuana, however, Gov. Susana Martinez vetoed the measure, noting that the addition of OUD as a qualifying condition was problematic since “the bill does not define what ‘treatment’ for opioid dependence entails.” In November 2017, the state’s Medical Cannabis Advisory Board recommended the addition of OUD as a qualifying condition again for medical marijuana use, and the measure is now in the hands of the state’s health secretary. Meanwhile, legislature memorials have been introduced in each chamber in support of allowing medical cannabis use for OUD, with lack of access to MAT as one of the stated reasons.⁶

• New York: In June 2018, New York expanded its opioid replacement program, allowing "any condition for which an opioid could be prescribed as a qualifying condition for medical marijuana" use . According to a release,4 the New York Department of Health made additional improvements to its program, including adopting new regulations, authorizing five additional registered organizations to manufacture and dispense medical cannabis, adding chronic pain and PTSD as qualifying conditions for its use, permitting home delivery, and empowering nurse practitioners and physician assistants to certify patients for its use.

• Arizona: A bill to allow medical marijuana as a treatment for OUD was introduced in 2018.⁶Currently, Arizona state law allows doctors to prescribe medical cannabis to patients who suffer from cancer, glaucoma, HIV, hepatitis C, Crohn's disease, severe nausea, PTSD, and chronic pain.⁷

• New Hampshire: In January 2019, New Hampshire lawmakers heard testimony on a bill to add opioid addiction as a qualifying condition to the state's medical marijuana program. New Hampshire’s medical marijuana law was enacted in 2013, and, according to a news report,⁸ houses 7,120 patients, 449 designated caregivers, and nearly 1,000 certified providers.

Other considerations in states such as Massachusetts and Maryland have been made as well.