In The CBD Story – Part 1, we explored what CBD is, CBD and the endocannabinoid system (ECS), and how ECS dysfunction can negatively impact health. We saw how CBD is an important modulator of the ECS that might help to restore balance when the ECS is disrupted by things like stress and poor diet. Here, we explore the effects of CBD in the body, and the role of CBD in several clinical conditions.
What are the Effects of CBD in the Body?
The complexity of CBD’s physiological effects increases exponentially when you consider that while CBD is clearly involved with the ECS, it actually has more than 65 molecular targets in the body1. Of these, approximately 49% are enzymatic, 20% are membrane and cellular transporters, 15% are receptors, and 15% are ion channels1. CBD is said to exhibit “promiscuous pharmacological activity” because it affects such a wide range of receptor targets, including the serotonin, adenosine, opioid, and dopamine systems2. Cannabinoid receptors, which CBD affects both directory and indirectly (through effects on AEA and 2-AG levels) also modify the release of many types of neurotransmitters, including those that both increase and decrease synaptic function, through a type of retrograde signaling3. As such, it is not surprising that CBD has been found to exhibit widespread effects in the body.
CBD has been reported to help with a vast array of health concerns. While people are understandably skeptical about how a single molecule can be of benefit in so many seemingly different ways, this can be explained by the widespread involvement of the ECS in virtually all systems in the body. In fact, scientists from the National Institutes of Health declared in 2013 that “modulating endocannabinoid system activity may have therapeutic potential in almost all diseases affecting humans.”4 However, not all of the claims made about CBD’s benefits are well supported by research evidence. Here, we present the most current research for some of the most well-investigated conditions.
Pain research to date has been heavily focused on the use of THC and a combination of THC and CBD, rather than CBD in isolation. As such, the majority of research comes from pre-clinical models, which has shown very promising results. In animal models of pain conditions that widely affect humans, including arthritis5,6 and myofascial pain7, CBD has been shown to be a safe and effective treatment. In fact, a recent review article stated that there is an “overwhelming” body of preclinical research supporting the use of CBD for pain8. Based on existing research, a group of expert clinicians recently rated the CBD in the treatment of chronic neuropathic pain at 75/100. In contrast, oxycodone scored in the 40s, and morphine and fentanyl in the 30s9.
CBD is widely promoted as a sleep aid, although research has also shown that it can also promote wakefulness. Whether CBD is sedating or alerting seems to depend on dose. A recent article reviewed the research on CBD’s wakefulness and sleep promoting effects and concluded that low to moderate doses are stimulating, while high doses are sedating10, although it should also be noted that the dose effects of CBD on sleep in humans have not been thoroughly investigated. CBD may additionally benefit sleep by reducing anxiety10,11, and it appears to help people with Parkinson’s Disease suffering from REM Sleep Behaviour Disorder12.
Human studies that have used CBD to treat anxiety disorders have shown benefit. CBD reduced anxiety in adolescents with SAD13 and in adults with social phobia in a simulated public speaking environment14. Similarly, CBD combined with medication and psychotherapy reduced the severity of PTSD symptoms in adults after eight weeks15, and PTSD anxiety was also reduced in a 10-year old child treated with CBD for four months16. And, in a study of psychiatric patients experiencing both anxiety and sleep concerns, nearly 80% showed a reduction in anxiety within the first month that was sustained over several months17. Several studies have also demonstrated CBD’s ability to reduce anxiety in healthy subjects. CBD effectively reduced anxiety in healthy adults placed in a simulated public speaking environment 18,19. Two other studies in healthy subjects found that CBD decreased anxiety, while at the same time showing changes in brain areas involved in the control of emotions20,21. There is some evidence that the effect of CBD on anxiety is U shaped, with efficacy at intermediate but not low or high doses22,23, although this finding is not unequivocal, as high doses of CBD also reduce anxiety in some studies23.
Most research on CBD and depression has used a pre-clinical rodent model. In these studies, CBD has consistently been found to be very effective in reducing depressive behaviour. CBD has also been found to induce positive changes in rodent brains, such as increasing the growth and development of new brain cells24. Given the positive effects of CBD in animal models of depression, and its interactions with multiple systems involved in depression, CBD has been proposed as a possible “novel antidepressant”25. Although limited, observational human research has also been positive, with a recent study finding that among 400 patients who reported using CBD to achieve “mood-improving” effects, 250 reported that CBD worked “very well by itself”26.
Topically applied CBD has shown to be beneficial in the treatment of many dermatological conditions. In humans, application of a CBD enriched ointment on the skin of 20 patients with psoriasis, atopic dermatitis, or scars resulted in improved hydration, transepidermal water loss, and elasticity when used twice daily for three months. Other improvements were noted in some patients, including reduced skin blemishes, scars, papules, pustules, and psoriasis27. Similarly, a small study of three pediatric patients found that topical CBD applied as an oil, cream or spray by their parents reduced pain and blistering and improved wound healing in patients with epidermiolysis bullosa28. In animals, CBD was found to reduce inflammation in a mouse model of ear irritation29, as well as research with human skin cells, which found that CBD inhibited the release of mediators involved in inflammation and wound injury30. Research with human skin cells has also found that CBD reduces sebum production and inflammation, suggesting a possible application in the treatment of acne31.
CBD has been well researched for its role in reducing seizures. As previously mentioned, the prescription drug Epidiolex has FDA approval to treat two rare forms of childhood epilepsy (Dravet and Lennox-Gastot syndromes), as well as for the treatment of seizures in tuberous sclerosis, a rare genetic disease. Epidiolex consists of highly concentrated CBD oil in a suspension with sesame seed oil, ethanol, strawberry flavor, and sucralose. In these conditions, Epidiolex is used as an adjunct treatment along with other medications32. CBD’s ability to reduce seizures is thought to relate not to effects on cannabinoid receptors, but rather via effects on other targets such as ion channels such as TRPV1 and neurotransmitter receptors33. Although the majority of clinical studies have focused on treatment resistant epilepsy in infants, children, and adolescents, some studies have also included adults, with a reduction in seizure frequency seen across demographic groups34. Interestingly, a 2018 meta-analysis found that compared to patients using purified CBD (usually as Epidiolex), patients using a CBD rich cannabis extract reported using lower average doses and reported fewer adverse events35.
In the last three years there has been an increasing amount of research attention focused on the use of CBD in the treatment of autism spectrum disorder (ASD), although clinical research is limited. Most studies have used CBD with a very small amount of THC. In one study, 1/3 of children with ASD who took cannabis oil containing 30% CBD and 1.5% THC reported benefits36. In another study, there was an overall improvement of 74.5% of children with ASD taking a ratio of 20:1 CBD:THC37, while a retrospective study of children with ASD taking CBD-rich cannabis also found improvements in the majority subjects38. It should be noted, however, that many parents of children in these studies reported side effects such as restlessness and sleepiness, and a small number of children in the studies worsened with treatment. The improvement of autism symptoms may relate to the ability of AEA to influence oxytocin, with increases in AEA activity at CB1 receptors improving social impairment in a rodent model39.
CBD is currently recommended in the management of Alzheimer’s Disease (AD) by organizations such as Dementia Care Central, a consumer education program, although others (such as the Alzheimer’s Society) are quick to point out the lack of clinical research in this area. While limited to pre-clinical research, findings from recent studies are extremely encouraging. In research conducted almost 15 years ago, CBD was found to reduce brain inflammation associated with injection of human beta-amyloid, the protein that causes the characteristic plaques, in a mouse model of AD40. Subsequent research showed that CBD can enhance the growth and development of new brain cells, reduce the abnormal responses of glial cells in the brain, and reverse and prevent the development of cognitive deficits in animal models41. More recently, in an in vitro model of AD using human hippocampal neurons (the part of the brain most associated with memory), application of CBD was able to reverse deficits in cellular mechanisms42. Similarly, it was found to extend the lifespan and healthspan in worms genetically modified to express human beta-amyloid43. In healthy humans, CBD has been found to improve blood flow in the brain, which is reduced in AD patients44. This suggests that effects on blood flow may be another of CBD’s brain protecting mechanisms. The rate of publication of studies related to CBD and AD is increasing rapidly, and this is an incredibly active area of current research.
As already mentioned, CBD appears to help people with Parkinson’s Disease (PD) suffering from REM Sleep Behaviour Disorder12, and it also may exert other benefits. PD is a movement disorder that involves dysfunction of the basal ganglia and several neurotransmitter networks, including dopamine, GABA and glutamate. The ECS, which plays a critical role in neurotransmitter modulation in the brain (especially via CB1), has emerged as a potential target in the treatment of PD, since CBD has been shown to influence brain neurotransmitters, reduce oxidative stress, and decrease brain inflammation45. Interestingly, the first research studies using CBD in PD treatment were done back in 1986, which showed that CBD helped to reduce side effects associated with levodopa treatment (the main treatment for PD that is associated with severe side effects) but did not help the disease itself46. Subsequently, CBD was found to decrease PD psychosis47, increase functioning and general well-being48, and decrease anxiety and tremor49. Several pre-clinical studies have also shown benefit, although clinical and preclinical research is not unequivocal45. It has been proposed that CBD might be helpful in early, but not late, PD, since later stages of the disease involve widespread death of dopamine neurons45.
This blog is the second in a three-part series on CBD. In The CBD Story – Part 3, we will explore the forms of CBD and CBD pharmacokinetics and safety.
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