Clinical pharmacology and therapeutics: “Cannabis in Cancer Care.”
Unlike many other cannabis oils, Rick Simpson Oil is high in tetrahydrocannabinol (THC), which is the main psychoactive chemical in marijuana. THC is the chemical in marijuana that provides the “high.”
Other research on THC and other cannabis compounds shows that they may kill off cancer cells while sparing healthy cells.
Other Medical Uses of Cannabis
Current Oncology: “Integrating cannabis into clinical cancer care.”
Cannabis is generally safe. Common side effects include dizziness or memory problems.
Karger Open Access: “The Trouble With CBD Oil.”
Cannabis oils that contain THC may help control nausea and vomiting for people who are going through chemotherapy. There’s also evidence that they can treat pain and improve appetite.
The CBD present in oils and other products is usually derived from fiber-type varieties of cannabis (hemp), because these are naturally higher in CBD content than drug-type varieties (marijuana). Although cultivation of hemp is allowed in many countries around the world, this is usually governed by strict regulations. After being banned for decades, hemp cultivation in the USA has only recently been reintroduced, and is still gearing up for full industrial production .
An important issue in the discussion around cannabis-derived oils is: how much THC is a legal CBD product allowed to contain in order not to be considered a narcotic? Authorities sometimes choose to deal with these regulations in a pragmatic way, recognizing that laws once designed to control marijuana abuse may not be fully applicable to hemp. For example, in the Netherlands, a maximum level of 0.05% THC is allowed in CBD products, even though, formally, any detectable trace of THC is illegal according to Dutch narcotics laws. This approach is based on the fact that even hemp varieties of cannabis produce a small amount of THC, and therefore naturally derived CBD extracts will carry some THC in the final products.
Legal Status of Hemp and CBD
Today, CBD is used for the treatment of a wide range of medical conditions. This started with the somewhat serendipitous discovery (by parents experimenting with self-medication for their children) that CBD had a therapeutic effect on a serious form of epilepsy in children, called Dravet syndrome . This effect is now under clinical investigation with the pharmaceutical CBD product Epidiolex®, which is currently in phase 3 trials with encouraging results [9, 10]. The media attention generated by its effect on severely ill children gave CBD the push needed to become a much desired medicine almost overnight . Other medical indications that may be treated with CBD, and are supported to some extent by clinical proof, include Parkinson’s disease , schizophrenia , and anxiety disorder . However, although research into the therapeutic effects of CBD is rapidly increasing, most current uses of CBD are not (yet) supported by clinical data. The popular use of these products means that physicians may be confronted with the effects of CBD oil even when they do not prescribe it themselves.
The discussion on the legal status of CBD revolves mainly around the question: is it a medicine or a natural food supplement? The main difference is that medicinal drugs are considered unsafe until proven safe, whereas food supplements are considered safe until proven otherwise. As a result, the central question becomes whether or not CBD is safe for consumers (children, elderly, patients) in large and unregulated quantities. Although there is only limited knowledge about the long-term effects of chronic use, or about drug-drug interactions between CBD and other medications , human studies have indicated that CBD is very well tolerated even up to a daily dose of 1,500 mg . Indeed, a recent World Health Organization (WHO) review concluded that “to date, there is no evidence of recreational use of CBD or any public health-related problems associated with the use of pure CBD” . However, the risks to be assessed about CBD products may not have much to do with the pure compound CBD itself, but more with the unknown composition and quality of the products offered. In particular, we should be looking into the presence of contaminants in these concentrated extracts, and into incorrect or even misleading labels for the cannabinoid content of products.
An excellent example is the use of CBD (and also THC) products for the self-medicating of cancer, with the intention of fully curing it . This is based on an increasing body of preclinical evidence showing cannabinoids to be capable, under some conditions, of inhibiting the development of cancer cells in vitro or in vivo by various mechanisms of action, including induction of apoptosis, inhibition of angiogenesis, and arresting the cell cycle . This is certainly exciting news, and research is ongoing around the world, but there is no solid clinical evidence yet to support that cannabinoids – whether natural or synthetic – can effectively and safely treat cancer in actual humans . In fact, there are indications that certain types of cancer may even accelerate when exposed to cannabinoids . This becomes problematic when patients choose to refuse chemotherapy treatment because they firmly believe in the rumored curative properties of cannabinoids. As a result, recommendation of cannabinoids for treating cancer should be done with great care, and with distinction as to the type of cancer being treated .
In contrast to the Δ 9 -THC-related cannabinoids, CBD has no known psychoactive effects, and therefore, has recently been the focus of intense research in many therapeutic areas, including cancer. At present, the Food and Drug Administration (FDA) has only approved Epidiolex, purified CBD, for use in patients with seizures associated with the Lennox-Gastaut syndrome or Dravet syndrome . Globally, more than 40 countries have approved medical marijuana/cannabis programs, whereas this is true of 34 states in the USA, plus the District of Columbia, Guam, Puerto Rico, and US Virgin Islands. While marijuana is considered a Schedule I controlled substance in the US, the Drug Enforcement Administration ruled that CBD is a Schedule V controlled substance . When approved by the FDA, CBD must contain less than 0.1% of Δ 9 -THC.
Evasion of the attack by the immune system is essential during the development of cancers. This is accomplished through dynamic interactions between different cytokines and their receptors in the tumor microenvironment. Tumors actively secrete different cytokines that attract a variety of infiltrating cells, such as TAMs, dendritic cells, MSDCs, and immunosuppressive regulatory T cells, which in turn help tumors to evade the attack by the immune system ( Figure 4 A). Cytokines released from myeloid cells can also induce genomic instability in tumor cells by directly damaging DNA or epigenetically altering the expression of genes ( Figure 4 B).
Kosgodage et al. showed that breast cancer cells treated with CBD had increased sensitization to cisplatin. CBD significantly decreased the release of exosomes and microvesicles (EMV) (at 100–200 nm), which typically aid the spread of tumors and cause chemo-resistance . However, in these same MDA-MB-231 cells, there was an increase in the release of the larger EMVs (201–500 nm). These cells displayed a concentration-dependent increase in ROS, proton leakage, mitochondrial respiration, and ATP levels. The authors attributed these effects to either a higher sensitivity or a sign of pseudo-apoptotic responses occurring, where the apoptotic factors such as ROS are still at a lower level resulting in the conversion of apoptosomes into EMVs. CBD inhibited paclitaxel-induced neurotoxicity through a 5-HT1A receptor system without conditioned reward or cognitive impairment . It also decreased the viability of both 4T1 and MDA-MB-231 cells. Thus, CBD may be a viable adjunctive treatment for breast cancers as it can sensitize cells, allowing for potentially lower doses of such toxic chemicals to be prescribed.
At this point, only one study testing CBD’s effectiveness on prostate cancer has been conducted in vivo. More quality studies using mouse models are required before moving to the clinical trial phase.
Nonetheless, toxic levels of ROS can induce cell death or autophagy in cancer cells. ROS modulate calcium channels, pumps, and exchangers activity by oxidizing their Cys residues . The increase of intracellular mitochondrial calcium or the oxidation of lipids damages the mitochondrial membrane resulting in the release of cytochrome c, a potent activator of apoptosomes [42,45]. ROS can also directly affect caspase activity and cleavage of Bcl-2, and/or increase the expression of cell death receptors such as TRAIL and Fas . Autophagy can be induced by the activation of the mTOR pathway.