Quick Hits

Welcome to Quick Hits! This is a new feature on Project CBD, where we collect some of the most interesting and informative tidbits of research into cannabis over the past week.

Combining CBD with Cancer Treatment

Posted: Marzo 18, 2019
cancer cell and lab tray with dropper

Scientists in at Western New England University in Springfield, Massachusetts, briefly review 10 studies that shed light on how CBD might interact with cancer treatments. Half of these studies examine how CBD can affect the metabolism and distribution of anticancer drugs, a topic Project CBD has been discussing for years. As the authors describe, large doses or regular use of CBD can both increase and decrease the levels of different drug-metabolizing enzymes called CYPs, which will alter the effectiveness of a pharmaceutical. At even higher doses, CBD can also modify the expression of certain proteins produced by cancers to resist chemo. In mice, CBD prevents or reduces neuropathy caused by the chemotherapy paclitaxel. (The condition where even mild stimulus causes pain is called allodynia.) The New England scientists also highlight a few papers in which CBD synergizes with chemotherapy, improving the survival from glioblastoma (a severe brain cancer) and multiple myeloma (a type of bone cancer). These interactions make clear that CBD can influence cancer treatment, but they don’t shed much light on how many people might be helped (or hurt), and how to identify those groups of people. Yet THC is already approved for treating wasting syndrome in cancer patients. Despite the schedule 1 status of cannabis, it behooves the medical community to set up trials that take advantage of the already-existent group of people using cannabis while treating cancer. There are some legitimate concerns and many compelling possibilities.

Cannabinoids in Brain Cancer

Posted: Marzo 18, 2019

Sometimes, science fails to see the tree for the forest. Statistical significance and double-blind trials are important, but so is human experience. Case studies are meaningful. Case studies often portend future discovery. So the case study of two Brazilian brain cancer patients who successfully combined CBD with their cancer treatment should not be dismissed. In their report, Paula Dall’Stella and other doctors in São Paulo describe the typical treatment plan for patients with glioblastoma. Patients who did not respond to the first treatment were given a drug cocktail called PCV along with CBD to reduce nausea. The authors highlight that «it is not possible to cure high-grade glioma patients … the aim of treatment is not only to prolong life, but also to prevent the deterioration of … quality of life.» These patients were still alive at the time the study was published, living longer than the median (15 months) after the diagnosis of glioblastoma. Both were able to play sports without excessive fatigue. These results don’t guarantee that everyone will find benefit from CBD, but it demonstrates that some people benefit significantly.

CB2 in Breast Cancer

Posted: Marzo 18, 2019

Breast cancers are often classified by the receptors they express. The three most common breast cancer receptors respond to estrogen, progesterone, or epidermal growth factor. The latter include HER2-positive breast cancers. Identifying these receptors facilitates treatment. A study led by scientists in Spain indicates that the endocannabinoid system plays an important role in the treatment of HER2-positive cancer. In fact, the cannabinoid receptor CB2 binds to HER2 — forming what is called a dimer — and this dimerization is associated with poor treatment outcome. When THC binds to the CB2 receptor, it breaks up this dimer. The researchers show, step by step, how this can kill the breast cancer cells. First THC binds to CB2, which splits apart the HER2-CB2 complex, as well as other HER2 complexes. This switches the secondary messengers — called G-proteins — that the receptors use to send signals into the cell. The cell starts to cut up its own HER2 receptors with a protein called c-CBL, which has an anti-tumor effect. Receptor dimers are increasingly being considered as targets for treating cancer, pain, schizophrenia, and numerous other conditions.

CBD in Lung Cancer

Posted: Marzo 18, 2019
blue and yellow drawing of lungs

Doctors in the UK recently reported the case of an elderly man who’s lung cancer responded to CBD. The man — being 81 years old — decided against chemotherapy or radiation, which would worsen his quality of life without much hope for extending it. Four months after a CT scan, the tumor cross section had shrunk to nearly one tenth of its initial size! The doctors — obviously surprised — found out that the patient had begun using a CBD oil 2-3 months earlier. He took 1.32 mg CBD twice a day for a week, then 6 mg CBD twice a day until the CT scan. He eventually stopped taking CBD oil because it caused mild nausea and had a bad taste. Please note: Project CBD does not endorse opting out of conventional treatment for the sake of using cannabinoids. Combining cannabinoids with cancer treatment seems very promising, but to try experimental therapy while refusing established treatments is dangerous.

Orphan Receptors in Cancer

Posted: Marzo 18, 2019

An «orphan receptor» is the term for a receptor in the body whose natural activator is not known. GPR55 is a G-protein coupled orphan receptor that interacts with the other cannabinoid system. CBD appears to inhibit GPR55, while endocannabinoids may activate it. Researchers in the UK and Italy collaborated on a study of GPR55 in pancreatic cancer. Activating GPR55 increased the proliferation and metastasis of cancer cells, while inhibiting GPR55 with CBD or another molecule slowed tumor progression. Mice treated with CBD and the chemo gemcitabine survived nearly three times longer than the mice that didn’t receive CBD. Since CBD affects many different proteins, it’s hard to be sure that GPR55 is the main reason for CBD“s protective activity. The scientists emphasize that CBD and gemcitabine — which are both approved for use in humans — should be tested in clinical trials. Previous research has shown that activating GPR55 stimulates the immune system, opposing the anti-inflammatory immuno-modulating effect of the CB2 cannabinoid receptor.

THC & Night Sweats

Posted: Marzo 18, 2019

The first medical use of THC allowed by the FDA was the 1985 approval of isolate THC (Marinol) to treat nausea and vomiting from chemotherapy. Since then, research has demonstrated numerous possible applications of THC and cannabis in cancer patients, including painkilling, protecting the brain from toxic chemo, and even synergizing with the treatment itself. Doctors in California recently presented case reports from five cancer patients with night sweats, showing that these individuals could manage their symptoms by ingesting pure THC. Four of the five patients swallowed 5 mg of THC or less at bedtime. After one week, one patient stated, «This is the first time I haven’t been waking up all drenched.»

Combining CBD with Anti-Epileptic Drugs

Posted: Marzo 12, 2019

Cannabidiol (CBD) is an astonishingly safe drug. Currently, the biggest safety concern is that at high doses it can alter the metabolism of other pharmaceuticals. That means CBD might amplify the toxicity of other drugs. This has come to a fore with epilepsy treatment, since overdosing anti-epileptic drugs (AEDs) is very dangerous. GW pharmaceuticals, the sole producer of pharmaceutical CBD available in the United States, recently published another study of how high doses of pure CBD (1500 mg/day) and AEDs might interact in adults. CBD tripled the exposure to the active metabolite of clobazam. It slightly increased (by ~25%) the exposure to an AED called stiripentol. And it did not appear to affect valproate levels. GW“s scientists also examined the converse: how do these three AEDs affect the body’s metabolism of CBD? Clobazam increased the levels of CBD and its metabolites by 30-50%. (CBD“s metabolites may confer anti-epileptic activity in and of themselves.) Stiripentol appeared to decrease the patients“ exposure to CBD by 20-30%, indicating stiripentol primed the body to metabolize CBD faster. And valproate didn’t seem to interact with CBD, at least not metabolically. These results are similar to previous research. It reaffirms that even very large doses of CBD can be used safely with anti-epileptic drugs. The study also provides support for using CBD as a first-line treatment, rather than a last resort: adding new medications to a CBD regimen had a minor or negligible effect on the breakdown of CBD. These data indicate that new drugs can be safely added to a CBD regimen. As with earlier research, CBD seems to most significantly affect clobazam, although the two drugs can be combined safely and effectively. There are still concerns regarding the interaction between CBD and valproate, which can potentially cause liver dysfunction – that wasn’t seen in this cohort, but liver enzymes should be closely monitored in any patients taking valproate and CBD together. Finally, it’s important to recognize that metabolism is not the only indicator of how drugs interact. This study looked at the rate of adverse events (side effects) in each treatment group. Since each group only consisted of 10-15 people, the results should be taken as concerns for future research to address, not definitive conclusions. About 10% of participants experienced rashes, which were severe enough for 6% of the patients to withdrawal from the study.

THC Better than CBD?

Posted: Marzo 12, 2019

In clinical research, cannabis is often set up to fail. Federal restrictions privilege studying isolated molecules from cannabis over the plant itself. And even when cannabis research is done, scientists are often forced to use low-quality weed from the National Institute of Drug Abuse. Because of this, most of the useful medical data on cannabis comes from observational studies, where people consuming cannabis are asked about their experience. Researchers in Albuquerque recently analyzed an app-based survey of over 3,000 cannabis users. They found that higher THC levels predicted better symptom relief for most problems (including anxiety and depression, but not all kinds of pain). CBD levels were not related to symptom relief, on average. This format for research, however, is likely biased. THC provides an immediate and obvious effect, whereas CBD may confer its effects with more subtlety. We don’t know how people found the app, or even that the app developers gave all the data to the researchers, so these results might not be representative of the medical marijuana community in general. The scientists are forthcoming about limitations of the study. However, they only report the correlation between cannabinoids and symptom relief for three conditions, not all 27 conditions surveyed. And because the data are owned by the app developer, we cannot interpret the results beyond what the authors have chosen to present. Despite these caveats, the study highlights a significant medical value of THC.

This is Your Brain on Drugs

Posted: Marzo 12, 2019

According to a recent study by University of Pensylvannia scientists, there were «small or limited associations between [adolescent] cannabis use and structural brain measures.» But even calling the effect small is aggrandizing harms. Their data didn’t support the notion that teens using cannabis causes any changes in the developing brain. The report goes on to say that «Detailed studies of vulnerability to structural brain alterations and … long-term risk are clearly indicated,» which is directly refuted by their own data. A few days earlier, another study from the University of Colorado Boulder found that a few brain regions are larger in adult cannabis user, though this wasn’t associated with different cognitive abilities.

Loss of Cannabinoid Receptors in Adenomyosis

Posted: Marzo 11, 2019
Drawing of woman with abdominal pain
Adenomyosis is a menstrual complication that causes heavier bleeding and pain during a woman’s period. About one in five women suffer from it. As with most female diseases, it is poorly studied and consequently hard to treat. The endocannabinoid system (ECS) is known to be involved in reproductive tissues, and it is dysregulated in pathologies like endometriosis, so it makes sense to consider the ECS in this condition. A recent publication by Chinese scientists suggests that adenomyosis is associated with lower levels of cannabinoid receptors in uterine tissue. The researchers took tissue samples from 45 middle-aged women suffering from adenomyosis, as well as healthy controls. The two primary cannabinoid receptors, CB1 and CB2, were expressed at significantly lower levels in the group of women suffering from adeonmyosis. This alone doesn’t tell us whether the ECS is protective or harmful: Is the loss of cannabinoid activity contributing to the disorder? Or is the body suppressing the ECS to protect itself? We would need new experiments to answer these questions. But there’s reason to believe that the loss of CB1 would cause problems. CB1 levels normally fluctuate throughout the menstrual cycle, yet there was no discernible variation for women who had been diagnosed with adenomyosis. And the lower expression of CB2 could lead to greater inflammation and pain.