Cannabinoids found in cannabis, such as tetrahydrocannabinol (THC) and cannabidiol (CBD), have shown anticancer effects in cell culture and animal models (but paradoxically also accelerate the growth of others). However, none of these research prove that cannabis may prevent or treat cancer (many drugs look great in cell cultures and animal models but fail in definitive clinical trials). Two preliminary clinical studies using cannabis for the treatment of brain cancer have been reported, and one of them shows promise for treating a particularly deadly form of the disease with little toxicity. Saying that cannabis can heal all forms of cancer is irresponsible and perhaps hazardous. Also, there’s evidence to suggest that delaying conventional therapy in favor of alternative methods might have a negative impact on cancer results. It is reasonable to use as an integrative treatment for those indications given its demonstrated benefits in helping treat cancer side effects like loss of appetite, neuropathic pain, and nausea; however, it should not be used in place of conventional therapy, especially in situations where curative intent is desired.
Wish cannabis could eliminate cancer altogether. I really hope this is just me wishing it into being. As oncology caregivers, our hearts are filled with delight when our patients achieve remission and with pain when they experience relapse. All of us in the medical community would be thrilled if our patients could have higher success rates and fewer negative reactions to treatment.
I have been treating patients with AIDS-related cachexia, chronic pain, nausea, and loss of appetite due to cancer or chemotherapy for the past 18 years, and I have found that all of these conditions respond very favorably to cannabis or its psychoactive ingredient delta-9-tetrahydrocannabinol (THC). When the results of these cases showed the possibility for a hitherto underestimated intervention, I published case reports of their amazing outcomes (for example, a case of Xeloda and graviola tea associated with a 5-year remission in a patient with metastatic breast cancer). I’ve promised publication of their case to many patients who’ve used cannabis or its isolates in the hopes that it will cure their metastatic sickness. However, I have not seen a single patient whose metastatic cancer miraculously went into remission after being treated with cannabis or cannabis products alone.
As a general oncologist at Zuckerberg San Francisco General Hospital and Professor of Clinical Medicine at the University of California, San Francisco, Dr. Donald Abrams has firsthand experience with medicinal cannabis in the state that first authorized it in 1996.
I have worked as an oncologist in San Francisco for 33 years, and I can state with confidence that the vast majority of the patients I have treated have taken cannabis in conjunction with their conventional medical therapy. That’s why I’d have a lot more survivors if cannabis worked to treat cancer. Although oncologists insist that the plural of anecdote is not evidence, most of my patients have probably used inhaled cannabis in the past, and so their plasma concentration probably does not approach that which can be achieved with the highly concentrated oil preparations (no data on this is currently available). The thing that makes me sad and upset the most is when a patient comes in for a consultation with a possibly curable malignancy but instead chooses to treat themselves with cannabis oil instead of traditional cancer treatments. However, there is currently no evidence to warrant making such a determination.
In spite of the uncertainty, Dr. Abrams writes, “What we do know is that cannabis is genuinely a great therapy for many cancer and treatment-related side effects—nausea, vomiting, lack of appetite, pain, melancholy, anxiety, sleeplessness.”
Since Dr. Abrams has been at the forefront of cannabis research in both HIV and cancer treatment, he will be able to summarize the scientific evidence on the advantages of cannabis and its isolates in a manner that no one else can during a SIO webinar on September 13, 2018. You’ll get an education in cannabis science, but you’ll also get insight into the political and social obstacles he faced in his pursuit of cannabis’s medical potential. I strongly advise you to register for this lecture (link below), which is free for SIO members and just $20 for non-members.
Though it’s true that cannabis isn’t a cure-all for cancer, there is preliminary evidence from cell lines and animal models that it may have an anti-cancer impact in people. While promising, it is important to keep in mind that the vast majority of medications that show promise in preclinical models fail to show any benefit in final human trials, including the reduction of cancer or the extension of life expectancy.
Please allow me to go over a brief refresher of cannabis 101 so that the language used in this blog is clear. Over 400 compounds have been isolated from the cannabis plant, the majority of which come from the two main species, C. sativa and C. indica. To keep things clear and straightforward, we may break down its parts into the following categories:
- Cannabinoids Non-Cannabinoids
- THC Terpenoids
- Cannabinoid (CBD) Flavonoids
- And more than a hundred others
In humans, there are two types of cannabinoid receptors: CB1, which is mostly expressed on neurons in the brain and central nervous system, and CB2, which is primarily expressed on non-neuronal tissues including immune cells. These receptors can also be expressed by cancer cells; however, there is conflicting evidence on whether this bodes favorably or poorly for prognosis. However, other studies have reported effects that are not prevented by inhibiting these receptors, suggesting that cannabis’ effects on cancer are not confined to contact with these receptors. Among cannabinoids, THC is the most well known for producing psychotropic and appetite-stimulating effects. Also known as CBD, cannabidiol (CBD) is another cannabinoid that has shown promise in cancer research.
Some synthetic (cannabinoid-based) medications like dronabinol (Marinol and Syndros, delta-9-THC), and nabilone have been authorized by the FDA (Cesamet, THC-similar). The FDA approved Epidiolex (cannabidiol naturally produced from cannabis) on June 25, 2018, making it the first non-synthetic cannabinoid to be authorized in the United States. It is used to treat two uncommon and severe types of epilepsy. Health Canada approved nabiximols (Sativex) in 2005 for the symptomatic treatment of neuropathic pain and in 2010 for the symptomatic reduction of muscular spasticity in people with multiple sclerosis; this was the first cannabis medicine to get regulatory clearance in North America. Nabiximols is a cannabinoid and non-cannabidiol rich extract of Cannabis sativa with a 1:1 THC:CBD ratio.
Both terpenoids and flavonoids, which give plants their color and scent, perform important biological roles. For the sake of brevity, we will not be discussing these two classes of chemicals in relation to cancer in this blog post, with the exception of the entourage effect, which will be discussed at the very end of this blog.
The example of Rick Simpson is the one that my patients bring up most frequently when we talk about anecdotal evidence (and yes, I regard anecdotal evidence as proof, but not of very high quality if it is not consistently duplicated in others) for the anti-cancer properties of cannabis. According to online sources, Rick was diagnosed with several basal cell carcinomas of the skin (not metastatic) and, after reading about the promising results of cannabis oil in preclinical studies, decided to apply the oil topically to his lesions and leave the bandage on for several days to treat his skin cancer. They (the lesions) went away. Even if the oil really was the cause of the remission, we still don’t know if it was a placebo effect (remember that it is also well known that duct tape can cure warts, but no more so than placebo), correlation not causation (did he or those who have followed suit receive any other intervention? ), or if it was worth researching in the treatment of basal cell carcinomas.
At best, extrapolating from this case (and the preclinical evidence) that cannabis oil is a suppressed cure for all types and stages of cancer is an educated guess; at worst, it’s a delusion that’s gone viral on the internet and is endangering the lives of patients with curable cancer who might choose to take cannabis oil instead of conventional therapy without any scientific follow-up with imaging or surgery. While the cell line and animal model studies imply that skin malignancies may have decreased angiogenesis (blood vessel formation) mediated by CB1 and CB2 receptors, Rick Simpson’s case report does deserve additional inquiry (Casanova et al).
As of this writing, only two prospective clinical studies have been conducted to examine the potential anti-cancer effects of cannabis or its derivatives. Antiproliferative effects were shown in some of the 9 patients who underwent intracranial injection of THC into an aggressive brain tumour termed glioblastoma multiforme, according to a phase I (preliminary trial to determine safety of the novel intervention) study done by Guzman et al (though not due to the THC).
The second research (Twelves et al.) has only been presented as an abstract so far; the entire manuscript has not yet been published. Patients with recurrent glioblastoma multiforme in this randomized, double-blind, placebo-controlled study were randomly assigned to receive either temozolomide (Temodar) chemotherapy and placebo or temozolomide with a 1:1 THC:CBD oro-mucosal spray, nabiximols (Sativex). The original plan called for just 20 participants to participate in the study’s randomization phase. Since the major goal was safety and not tumor response, it is not possible to draw any firm inferences from these findings. An other red flag is that there was no justification for why 12 people were assigned to THC:CBD and only 9 to placebo in this trial. One patient can make a huge difference in a research of this size. One-year survival (i.e., the probabilities of being alive 1 year after starting the trial) was 56% in the placebo group and 83% in the THC:CBD group. Median survival was 369 days in the placebo group and >550 days in the THC:CBD group. There is preliminary evidence of safety when using nabiximols in conjunction with temozolomide, however more investigation is needed by conducting a bigger phase II trial.
Another popular theory is that cannabis’ anti-cancer effects are amplified by a synergistic “entourage effect,” in which the sum of the plant’s parts is larger than the sum of its parts alone. In a research published in 2018, Blasco-Benito et al. compared the anticancer effects of THC alone to those of a whole plant extract and found that the extract was more powerful than THC in cell culture and animal models of ER+, HER+, and triple negative breast cancer. Similarly, the extract was complementary to the chemotherapeutic drugs tamoxifen, lapatinib, and cisplatin in the treatment of breast, prostate, and pancreatic cancers, respectively. The authors also found that the extract’s heightened potency did not seem to be related to the 5 most prevalent terpenes, which is in line with the idea that the potency was due to the cannabinoid concentration. Should all breast cancer patients start using cannabis extracts after reading this study? Hardly. Keep in mind that only 10% of medications with promising results in cell cultures and animal models make it through human clinical trials, and over 50% of these failures are attributable to lack of effectiveness (Hay et al). However, these and other studies provide hope to cancer patients who opt to combine cannabis with conventional therapy in the hopes of minimizing treatment-related negative effects. Numerous preclinical investigations, for instance, have looked into the question of whether cannabis and chemotherapeutic drugs might have an antagonistic or synergistic effect. Briefly, synergy is the common thread in investigations with gemcitabine, temozolomide, paclitaxel, and 5 fluorouracil in cell cultures of pancreatic, glioma, gastric, lung, and colon malignancies (reviewed by Maida et al).
It’s important to keep in mind that not all cannabis studies show that they’re completely safe, since certain cancer cells grow more quickly in response to exposure and there may be immunosuppressive effects to consider as well. The immune system is thought to be less conducive to an effective anti-cancer immune response when cannabinoids interact with the CB2 receptor, which is mainly expressed on immune cells. This results in a decrease in interferon gamma production, a decrease in T-cell proliferation, and a shift from a Th1 to a Th2 profile. Other writers have done excellent work reviewing the pertinent papers (Sledzinski et al).
Use caution while using cannabis until it is known how these results will interact with immunotherapy (i.e. PD1/PDL1 inhibitors like nivolumab). In reality, Taha et al. evaluated the medical records of 140 patients who were treated with nivolumab for advanced melanoma, non-small cell lung cancer, or renal cell carcinoma in a retrospective observational research. Eighty-nine individuals were given nivolumab, while 51 were were given cannabis in combination with the drug. Cannabis use was the sole significant predictor of poor immunotherapy response, with rates of 37.5% for nivolumab and 15.9% for those who got both (odds ratio 3.13; 95% CI 1.24-8.13, p=0.02). However, cannabis had no influence on either progression-free survival or total survival. Considering the study’s retrospective nature and the various confounding variables, it should be seen primarily as a preventative study, and more investigation is necessary before any firm conclusions can be drawn.
In conclusion, scientific studies have revealed more about cannabis and its cannabinoid chemicals than ever before, and further study may lead to the establishment of medicinal indications for cannabinoids in the treatment of certain forms of cancer. To learn more about the clinical research that has helped de-stigmatize cannabis by showing its advantages in enhancing the quality of life of people coping with cancer and the symptoms associated with cancer treatment, please join the forthcoming webinar by Dr. Donald Abrams. At the very least, you will have gained a deeper understanding of how important research is in empowering people to make better choices about their health. If you happen to come across this post too late to attend or are unable to do so for any other reason, Dr. Abrams has written a number of highly recommended pieces, all of which are referenced at the bottom of this post. More studies will show how we can best use cannabis or its isolates/derivatives for medicinal reasons as legalization of medical marijuana spreads throughout North America, guaranteeing a future with fewer treatment side effects, a higher quality of life, and a greater chance of a cure.