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cannabinoid complex reviews

Yadav V, Bever C Jr, Bowen J, et al. Summary of evidence-based guideline: complementary and alternative medicine in multiple sclerosis: report of the guideline development subcommittee of the American Academy of Neurology. Neurology. 2014;82(12):1083-92. View abstract.

Valvassori SS, Elias G, de Souza B, et al. Effects of cannabidiol on amphetamine-induced oxidative stress generation in an animal model of mania. J Psychopharmacol 2011;25(2):274-80. View abstract.

Uses & Effectiveness ?

Hurd YL, Spriggs S, Alishayev J, et al. Cannabidiol for the Reduction of Cue-Induced Craving and Anxiety in Drug-Abstinent Individuals With Heroin Use Disorder: A Double-Blind Randomized Placebo-Controlled Trial. Am J Psychiatry. 2019:appiajp201918101191. View abstract.

Massi P, Solinas M, Cinquina V, Parolaro D. Cannabidiol as a potential anticancer drug. Br J Clin Pharmacol 2013;75(2):303-12. View abstract.

McGuire P, Robson P, Cubala WJ, et al. Cannabidiol (CBD) as an Adjunctive Therapy in Schizophrenia: A Multicenter Randomized Controlled Trial.Am J Psychiatry. 2018;175(3):225-231. View abstract.

Almost overnight, CBD oils have become an interesting combination of popular holistic medicine, miracle cure, and a natural answer to the synthetic drugs dominating modern medicine. With CBD, patients receive the promise of being in control of their own ailments, and no longer feeling at the mercy of their treating physicians. This has turned out to be a particularly powerful message. Many patients use CBD oils freely for ailments both confirmed and self-diagnosed, and the rapid innovations with CBD products have actually been quite impressive. But while new CBD products keep entering the market virtually unchecked, effective regulatory control of these products has stayed far behind. As a result, unknown risks about long-term effects remain unaddressed, especially in vulnerable groups such as children, the elderly, and the chronically or terminally ill. It should be noted that this discussion goes well beyond CBD only, as new products containing additional cannabinoids like CBG, THCV, and acidic cannabinoids are following closely behind. We know even less about these compounds than about CBD, and very limited human safety data are available.

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 [15]. 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 [16]. 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 [17]. In fact, there are indications that certain types of cancer may even accelerate when exposed to cannabinoids [18]. 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 [19].

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.


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 [26].

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 [36], human studies have indicated that CBD is very well tolerated even up to a daily dose of 1,500 mg [37]. 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” [38]. 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.

Oil has become a favorite mode of administration for many medical users of cannabis and cannabinoids for multiple reasons. First of all, concentrated extracts allow the consumption of a large dose of cannabinoids in an easily ingestible form. With CBD oil, there is no risk of intoxication (getting high) [6], so much larger doses can be consumed than would be possible for THC-rich products. Many users who prefer the holistic approach of using herbal cannabis worry about the stigma associated with the typical smell caused by smoking or vaporizing it. Cannabis oil has no smell that may identify a consumer as a cannabis user, and it can be used discretely even in a social setting, e.g., at work or around family. Moreover, it can be efficiently dosed simply by counting the number of drops consumed. These same benefits of using a concentrated extract were identified in a large survey among medicinal cannabis users published in 2013 [7], perhaps as an early indicator of the emergence of cannabis oils as a preferred method of ingestion. Currently, the market is developing further towards more sophisticated and patentable products, including oral capsules, liposomal products, skin creams, and chewing gums containing CBD.

Although CBD seems destined to play an important role as a therapeutic agent for a growing number of medical indications, we should seriously ask ourselves if the current unregulated production and sale of CBD oils is done responsibly. Despite the fact that CBD is mainly sold as “just” a food supplement, it is often used by severely ill people with the intention of improving their body functions in a way that their standard medication could not. This obviously puts CBD uncomfortably close to the realm of medicines. Interestingly, the WHO, based on a review of available scientific data and input from international experts, recently concluded that CBD does not immediately require rescheduling as a drug [38], although a fuller review on the risks and benefits of CBD is still being planned. Nevertheless, perhaps the use of CBD products should be assessed in a broader perspective, to cover all ingredients used in the preparation, as well as any contaminants that are already known to be common in recreational cannabis.

Is there documentation that the patient has had failure of all other conventional medications to treat his or her ailment?

As with most cannabinoid research to date, conducting studies can be difficult due to limited legal access to medical grade marijuana and phytocannabinoid extracts. Hemp-derived CBD, however, has recently experienced less regulation and as a result research using CBD for refractory epilepsy has experienced a resurgence.

Δ9-THC has also been shown to protect the brain from various neuronal insults and improve the symptoms of neurodegeneration in animal models of MS, PD, HD, amyotrophic lateral sclerosis (ALS), and AD.[23,35,41] Like CBD, Δ9-THC can offer non-ECS protection by direct effect on neuronal cells, and nonneuronal elements within the brain. Mechanisms include modulation of excitatory glutamatergic transmissions and synaptic plasticity, modulation of immune responses, the release of antiinflammatory mediators, modulation of excitability of N-methyl-D-aspartate receptors and its effect on gap junctions, calcium, and antioxidants.[70]

Adverse effects

CBD acts specifically to enhance adenosine signaling which increases extracellular adenosine, not AG-2. Neuroprotective effects of CBD in hypoxic–ischemic brain damage also involve adenosine A2 receptors. Specifically, CBD diminishes inflammation in acute models of injury and in a viral model of MS through adenosine A2 receptors.[15,18,72,78] CBD also ameliorates the severity of the disease by attenuating neuroinflammation and axonal damage through an effect on oligodendrocyte progenitor cells (OPC) that can be used to differentiate into new myelinating oligodendrocytes. OPCs are highly vulnerable to inflammation and oxidative stress. Inflammation contributes to demyelinating diseases such as MS. Synthetic cannabinoids studies have shown they can protect OPCs possibly by controlling endoplasmic reticulum (ER) stress response that modulates the response to inflammatory stimuli.[79]

Despite the preclinical data by GW Pharmaceutical and anecdotal reports on the efficacy of cannabis in the treatment of epilepsy, a 2014 Cochrane review concluded that “no reliable conclusions can be drawn at present regarding the efficacy of cannabinoids as a treatment for epilepsy.” This report noted this conclusion was mostly due to the lack of adequate data from randomized, controlled trials of Δ9-THC, CBD, or any other cannabinoid in combination.[28,38,43,83]

In 1980, Cunha et al. reported anticonvulsant benefits in 7/8 subjects with medically uncontrolled epilepsy using marijuana extracts in a phase I clinical trial. Since then neurological applications have been the major focus of renewed research using medical marijuana and phytocannabinoid extracts.

Δ9-THC can mediate the effects of the neurotransmitter serotonin by decreasing 5-HT3 receptor neurotransmission. This can contribute to the pharmacological action to reduce nausea. This effect can be reversed at higher doses or with chronic use of Δ9-THC.[103,117] Synthetic analogs of Δ9-THC, nabilone (Cesamet, Valeant Pharmaceuticals North America) and dronabinol (Marinol-Solvay Pharmaceuticals), are prescribed for the suppression of the nausea and vomiting produced by chemotherapy.[87] There is limited use for synthetic Δ9-THC due to multiple side effects mediated through activation of CB1 on the CNS in this population.