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February 1, 2019

Should Physicians Recommend Replacing Opioids With Cannabis?

Author Affiliations
  • 1Veterans Affairs Health Services Research and Development Center
  • 2Stanford University, Palo Alto, California
  • 3Department of Community Health Sciences, Boston University School of Public Health, Boston, Massachusetts
  • 4Clinical Addiction Research and Education Unit, Section of General Internal Medicine, and Grayken Center for Addiction, Boston Medical Center, Boston, Massachusetts
  • 5Associate Editor, JAMA
JAMA. 2019;321(7):639-640. doi:10.1001/jama.2019.0077

Recent state regulations (eg, in New York, Illinois) allow medical cannabis as a substitute for opioids for chronic pain and for addiction. Yet the evidence regarding safety, efficacy, and comparative effectiveness is at best equivocal for the former recommendation and strongly suggests the latter—substituting cannabis for opioid addiction treatments is potentially harmful. Neither recommendation meets the standards of rigor desirable for medical treatment decisions.

Recent systematic reviews1,2 identified low-strength evidence that plant-based cannabis preparations alleviate neuropathic pain and insufficient evidence for other types of pain. Studies tend to be of low methodological quality, involve small samples and short-follow-up periods, and do not address the most common causes of pain (eg, back pain). This description of evidence for efficacy of cannabis for chronic pain is similar to how efficacy studies of opioids for chronic pain have been described (except that the volume of evidence is greater for opioids with 96 trials identified in a recent systematic review3).

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3 Comments for this article
Cannabis Problematics Include but are not Limited to Pain Management
Albert Reece, MBBS,MD,FRCS(Ed.), FRACGP | University of Western Australia, Edith Cowan University, Perth, Australia
The Viewpoint by Humphreys and Saitz, whilst correct, does not address the weightiest objections to cannabis dissemination implied by recently published research (1).

Awasthi showed that loss of glutamate A2 AMPA receptors, the main excitatory receptor of the CNS, is directly associated with forgetfulness in a mouse swim model, findings with direct relevance to neurodegenerative diseases including Alzheimers (2). Dejanovic showed that loss of synapses was also directly related to forgetfulness in a transgenic mouse model of complement- and microglial-mediated forgetfulness of tau-associated dementias including clinical Alzheimers (3).

These newer studies bring into precise focus
recent work in the cannabis field showing that adolescent cannabis exposure results in loss of whole dendrites including synapses (4) and a reduction in post-synaptic glutamate A2 AMPA receptors (5). These studies clearly relate to the well-established Hebbian model of synaptic transmission from 1946 which relates the strength of synaptic transmission to neural activity - and its inverse.

Other work relates tetrahydrocannabinol-mediated disruption of stathmin signalling not only to axonal growth cone steering errors, but more recently to impaired neurogenesis, spinogenesis and NMDA-receptor mediated memory formation.

Cannabis dependence is notable for its wide spectrum of clinical presentations including psychiatric, respiratory, immune, cardiac, vascular, bony, reproductive and malignant manifestations.

Cyclic-AMP Response Element Binding protein is known to be a key target of addictive drugs including cannabinoids and directly regulates the sirtuin group of histone deacetylases which are amongst the best documented epigenetic modulators of organismal multi-system aging; and direct interactions between cannabinoids and sirtuins have been described.

Tetrahydrocannabinol, cannabidiol and other cannabinoids have prominent epigenetic footprints transmissible through human and rodent sperm for several generations (5).

The USA hosts an autism epidemic which is growing nationwide in quadratic manner (Individuals with Difficulties Education Act). Cannabis is an obvious suspect.

Moreover one notes that atrial septal defect (secundum) (ASD) is growing exponentially in high cannabis use states of Alaska, Colorado and Kentucky but declining in conservative states (National Birth Defect Prevention Network).

Since ASD has only been linked with prenatal cannabis use in one previous study, this implies that our knowledge of cannabis teratology is incomplete, and likely to increase rapidly given increased use, THC concentration, activity via the paternal line, involvement of numerous cannabinoids, and now entry into the food chain following the US Farm Act.

Cannabis-induced neurodegeneration and aging apparently applies to humans at all developmental stages – as gametes, in utero, childhood, adolescence and adulthood.


1. Humphreys K, Saitz R. Should Physicians Recommend Replacing Opioids With Cannabis? February 1, 2019.
2. Awasthi A. et al. Science. 2019;363(6422).
3. Dejanovic B. et al.. Neuron. 2018;100(6):1322-1336 e1327.
4. Miller ML., et al. Mol Psychiatry. 2018.
5. Szutorisz H, et.al. Neurotoxicol Teratol. 2016;58:107-114.
This Is Wrong!
Jacob Mirman, MD, MD, DHt, CCH, MHom | Life Medical, Private Clinic in MN, Medical Director
I totally disagree with this opinion. Consider the following facts, that are mostly agreed upon:

- We are having an opioid epidemic fueled by opioid prescriptions. Many deaths!
- Cannabis is very safe. Overdose is not an issue. No deaths from overdose.

I have certified about 1,700 patients for medical cannabis since 2015. I see them all for follow-up every year, as is MN law. The main qualifying conditions are pain, PTSD and inflammatory bowel disease. The MN Dept of Health is running a study and has already reported that cannabis is very effective
in pain, a finding borne out in my practice. Many patients say their life turned around when they started on cannabis. Their pain is better, they are happier, they sleep much better, and are able to be more active. PTSD symptoms are much better and UC and Crohn's disease essentially go into remissions in many cases. Many stop their drugs, including opioids, which were giving them side effects, or dramatically reduce them. I have never seen a single drug do so much and with a favorable side effect profile.

There are some patients who don't like it, mostly the elderly, who get more side effects. And many people can't afford it, which is a shame. But overall the Minnesota program is phenomenal.

All I can say to the detractors, those waiting for some big studies, is 'Come and see.' Once we know a treatment is safe, we can use it. And the experience in my clinic speaks for itself. It is unethical to withhold this therapy from suffering people.
CONFLICT OF INTEREST: I Certify People for Medical Cannnabis Under MN Law
Cannabis Might be Used in Limited Circumstances
Beth M, LCSW | University-affiliated Clinic
Interesting article. Maybe this could work with opiate-naive patients, but to think that taking a patient off either opioid pain management or methadone maintenance is very premature. You would need a patient who is extremely dedicated to abstinence because most patients realize that cannabis is not going to take away the withdrawal symptoms. What would the answer be for patients craving opiates?