Medical cannabis research is coming thick and fast in the 21st century, as scientists all over the world make up for decades of lost time due to prohibition. Scientists have now realized that cannabinoids from the plant interact with receptors that are part of a larger system in the body: the endocannabinoid system (ECS).
Cannabinoid receptors are present in the central nervous system (CB1 receptors) and the peripheral nervous system (CB2 receptors), and these transmit messages from endocannabinoids and cannabinoids to regulate appetite, immune system response, mood, cognitive function and more. However, these cannabinoids have contrasting properties. While tetrahydrocannabinol (THC) is psychoactive, cannabidiol (CBD) is not intoxicating whatsoever, and therefore has wider appeal, particularly among children, seniors and other vulnerable demographics.
But recently, researchers have discovered that some cannabinoids, including CBD, affect receptors outside of the ECS, and that these interactions partially explain some of the compound’s therapeutic effects. For instance, the peer-reviewed medical journal PAIN published a study from the McGill University in Quebec, Canada, in 2018, which identified new mechanisms behind CBD’s pain-relieving and anti-anxiety properties. The research was carried out on rodents, which are often used as precursors to humans in neurological studies because of brain similarities.
CBD has long been noted for its anxiolytic qualities, with an Italian investigation in 2011 finding that large doses of the cannabinoid in capsule form helped to improve public speaking performances in participants who had never previously tried treatment for their anxiety. However, just why CBD has such a marked effect on anxiety has long been inconclusive.
Studies have shown that CBD has a calming effect on the brain, reducing the number of nerve impulses transmitted, and therefore the number of thoughts, by facilitating an increase of gamma-Aminobutyric acid (GABA) into the brain. GABA is an inhibitory neurotransmitter that can bind to the required GABAA receptor more successfully when CBD is present, as the cannabinoid acts as a positive allosteric modulator on the receptor, which enhances its binding affinity. As a result, the imbalance between inhibition and excitation in the brain is corrected, reducing racing thoughts which are typical in manic episodes.
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But research has also found CBD to be a partial agonist of the serotonin 1A receptor (5-HT1A) in the serotonin system, which is often a target for drugs intended to relieve anxiety and depression. The importance of this in regard to CBD’s anxiolytic properties was largely unknown until the paper published in PAIN.
The researchers administered CBD intravenously to the rats over a seven-day period, which was enough to reduce anxious symptoms. The dosage was gradually increased and served to reduce the firing rate of 5-HT neurons in the dorsal raphe nucleus. A week of CBD treatment helped to normalize 5-HT neuronal activity.
This could potentially be a significant breakthrough for anxiety medication, considering that selective serotonin reuptake inhibitor (SSRI) drugs, which are typically a first-choice, can take a fortnight or longer to show benefits.
The study’s lead author Dr Gabriella Gobbi said that their findings showed that CBD could be used as a medicine on its own, and that the “dangerous side effects of THC” could be avoided. For anxiety, this could be very important, as the unpredictable mind-altering impact of the mind-altering chemical has been known to exacerbate symptoms and also induce paranoia. Emotions can become more extreme under the influence of THC – this either works out positively, with euphoria and increased short-term happiness, or negatively with anxiety.
Since the research was on rats, nothing concerning dosage or intake method would be of use to humans, but many anxiety sufferers are already experimenting with various CBD products, and reporting substantial relief. Fast-acting solutions, such as CBD vape oil and e-liquid, are popular because they quickly suppress anxiety attacks, which are notorious for starting unexpectedly and worsening rapidly.
Chronic pain is a very common reason for taking medical cannabis, and campaigners are always keen for it to be a qualifying condition in any legislation, as it greatly expands the number of patients eligible for cannabinoid treatment. Moreover, the leading class of painkillers, opioids, have proven dangerous and addictive. In 2017, almost 50,000 Americans died from overdoses on either prescription opioids or illicit opioid drugs.
Research has long suggested that the ECS has a role to play in regulating pain, although scientists have been less certain on the mechanism. THC seems to have an important role in reducing the perception of pain by binding with the CB1 receptor – it’s feasible that the psychoactive effects are a distraction from the discomfort. As a non-psychoactive substance, CBD cannot ease pain in this way, but the study in PAIN has linked another receptor, outside of the ECS, to the pain relief process: the vanilloid receptor (TRPV-1).
The vanilloid receptor is involved with body temperature regulation, and also controls sensations of heat and pain. The endocannabinoid anandamide is an agonist of this receptor, and CBD has either indirect or direct influence. As CBD blocks the FAAH enzyme from degrading and therefore reducing anandamide levels, this may facilitate some pain reduction. The Canadian researchers noted that low doses of CBD had an analgesic effect on the rats via TRPV-1 activation.
These findings are ultimately still preliminary in view of CBD as a mainstream future treatment for chronic pain, and the next step is for clinical research on humans. However, this study has shown that cannabis-induced pain relief is possible, without the downsides of THC. For patients who are stuck on opioids and seeking alternative, this is important since CBD has been declared non-addictive by the World Health Organization (WHO), while around one in 10 users of cannabis containing THC end up becoming dependent on the drug. Hence, with CBD, there’s no risk of swapping one addiction for another.
The study featured in PAIN has filled in a couple more pieces of the medical cannabis puzzle. The more that scientists find out about the isolated properties of various cannabinoids, the easier it will be to develop treatments which target conditions without causing side effects. It is always encouraging when CBD is found to have a therapeutic effect, as while THC has some critical uses which other cannabinoids cannot produce, patients invariably prefer treatments that are neither intoxicating nor cause tolerance.