A writer asked me to respond to some questions about marijuana. Here’s what I wrote
1. Is there any evidence that cannabis has mental health benefits?
There is one high-quality paper (multi-center, randomized, double-blind, placebo controlled; American Journal of Psychiatry, March, 2018) that suggests cannabidiol (not cannabis) 1000 mg/day may be helpful as an augmenting agent (i.e. added to a patient’s antipsychotic medication) in schizophrenia. https://www.ncbi.nlm.nih.gov/pubmed/29241357
The evidence that cannabis has mental health benefits is largely anecdotal at this point.
The evidence that it causes harm, especially in the young, greatly outweighs the reports of benefits. See, for example, Terrie Moffitt’s Dunedin study, which followed over a thousand New Zealand kids for 38 years, and saw cognitive decline in adolescent onset users not reversed by cessation of use and suggested a neurotoxic effect of cannabis on the adolescent brain. (PNAS 10/2/2012)
https://www.pnas.org/content/109/40/E2657
2. Some argue that “Big Pharma” is afraid of the medical benefits of cannabis. Is there any truth to that?
Since at present there are few demonstrated medical benefits of cannabis, big pharma has nothing to be afraid of, and, I suspect, would be happy to develop patented products if anything interesting emerges, much as Johnson and Johnson has developed esketamine nasal spray after ketamine’s benefits became apparent.
The cannabis industry, on the other hand, has reason to be afraid of (and attempt to discount, ignore, minimize, and denigrate) the increasing reports of harm associated with cannabis use, following the tobacco, alcohol, and sugar industries’ playbooks.
See, for example, the recent review in JAMA Psychiatry of 11 studies covering about 23,000 patients, showing an odds ratio for suicide attempt of 3.54 in the cannabis users, and linking adolescent cannabis use with the development of depression and suicidality in later life (but, surprisingly, not anxiety). https://jamanetwork.com/journals/jamapsychiatry/fullarticle/2723657
3. Would you ever recommend someone use cannabis for mental health treatment? If so, why? If not, why?
No, because a doctor’s goal is to help his or her patients. Everyday life provides enough harm and pain without any need for help from the doctor. The evidence for harm from cannabis is pretty overwhelming today, on March 2, 2019.
That being said, since cannabis is easily available in California, my patients use it on their own quite frequently. When I ask them what they observe, those who observe benefit seem to find it helpful for relaxing in the evening. One patient, for example, found that 2-3 puffs of a largely indica blend helped him unwind and reduce the amount of Seroquel he needed to sleep.
4. Furthermore, would you ever recommend someone replace their mental health medication with cannabis?
Based on our present knowledge base, that would constitute malpractice, or an extreme deviation from the standard of care, since the evidence of benefit from cannabis rests on anecdote, the lowest level of scientific evidence. FDA approved medications need to demonstrate efficacy in at least 2 randomized, double-blind, placebo-controlled trials. Granted, the negative trials are usually not published, but that’s another story.
5. In a perfect world, how should cannabis be used medically, if at all?
Cannabis has moved rather quickly in the public’s perception from a schedule 1 controlled substance (defined as a drug with no currently accepted medical use and a high potential for abuse) to a putative medicine. But before it can be taken seriously as a medicine, we need high-quality data ( like randomized, double-blind, placebo-controlled trials) that show what it can do. At present, in my opinion it is similar to alcohol and tobacco, and best avoided.
Learning from Dr. Fauci
Listening to Dr. Fauci’s portion of the Covid 19 response team briefing on March 5, 2021 on MS-NBC gives the wonderful experience of being taught by a world-class scientist. He suggested some homework, reading an article by John P Moore, PhD. (JAMA 2021 published March 4, 2021). I will attempt to summarize the key points Dr. Moore makes.
Dr. Moore notes that South African and Brazilian variants (B.1.351 and P.1, the antibody and possibly vaccine resistant variants) have “sequence changes in key positions suggesting that they arose under neutralizing antibody selection pressure within people infected or previously infected with SARS-CoV-2. Unusual variants have been seen when the virus replicates at high levels for prolonged periods in immunocompromised individuals.”
He goes on to state that while a strong neutralizing antibody response suppresses virus replication, and a weak response does little to suppress replication, “neutralizing antibodies of intermediate potency are thought to cause the virus to evolve and create ways to escape the constraint on its ability to replicate.”
The “combination of a high virus replication rate within an individual (a high viral load) and a suboptimal level of neutralizing antibodies is the exact environment in which resistant viruses are considered likely to emerge and spread.”
Ominously, the B.1.351 variant was found (in lab experiments) to be partially resistant to neutralizing antibodies induced by 2 doses of the Pfizer mRNA or the Moderna mRNA vaccine. (Implication: don’t feel free to do what you want after 2 doses)
In 2 reports, single dose Pfizer vaccine serum antibodies could not neutralize B.1.351 at all.
Vaccines are less effective during the period between the first and the second dose, and when people are infected in this interval, “the virus can replicate in the setting of a suboptimal of neutralizing antibodies, a situation in which resistant variants may emerge”.
This argues for a short period between the 2 doses of Pfizer or Moderna, which is not the policy in the UK, where a variant of B.1.1.7 (the original is more infectious but not vaccine resistant) containing the E484K substitution in the S (spike) protein has been detected. The E484K substitution is considered a hallmark of neutralizing antibody resistance.
The single-dose Johnson & Johnson vaccine raises the concern that resistant viruses will arise in J&J vaccine recipients if the efficacy of the single dose “wanes over time”. As for giving a 2nd dose of the J&J vaccine, there is a possibility that antivector immunity (to the adenovirus that carries the antigenic material) compromises the efficiency of a second, identical adenovirus dose. Unlike the J&J and the AstraZeneca, which use the same adenovirus vector for each injection, the Russian Sputnik V uses different adenovirus vectors for each injection, and reportedly has higher efficacy.
The concept of “original antigenic sin” is a scenario in which a redesigned vaccine (eg to go after the E484K sequence change) “boosts only the original neutralizing antibody rather than eliciting a new set of antibodies that are intended to target the new virus variant.” Experiments are needed to determine if this applies. If it applies, it would complicate making upgrades to the vaccines we have now.
Thank you, Dr. Fauci, for this learning experience.