Cannabidiol (CBD) and tetrahydrocannabinol (THC) are both rising stars within the medical community as researchers uncover mounting evidence of efficacy and legal barriers to use are dismantled. However, many patients are unclear about the differences between the two chemicals. This is understandable, given their close relationship; both CBD and THC are produced in large quantities by the cannabis sativa and cannabis indica ferns and activate the cannabinoid receptor system, leading to partially overlapping mechanisms of action. However, the two chemicals have significant differences that inform both application and tolerability. For those who are interested in integrating cannabinoids in their treatment plans, understanding these differences is essential for optimizing therapeutic benefits while minimizing risk.
Investigating the Therapeutic Value and Challenges of THC
THC can produce a broad range of physiological and psychological effects, including euphoria, anxiolysis, calming of the stomach, hunger, divergent thinking, altered perceptions, and analgesia. While some of these effects primarily drive recreational use, others offer significant therapeutic value for patients experiencing health conditions such as chronic pain, anxiety, anorexia, nausea, and depression. This has led to widespread use of THC in not only the treatment of specific disorders and illnesses, but in palliative care and to alleviate the side effects of chemotherapy. THC has also been found to lower intraocular pressure in patients with glaucoma, but the short duration of this effect and subsequent need for frequent redosing prohibits it from being a viable treatment option for most.
THC is commonly consumed via inhalation of combusted cannabis, but many users—particularly therapeutic users—choose to consume THC via oils, food products, or vaporized liquid. The method of administration is a critical determinant of user experience, as it informs both the rate of absorption and duration of action. When consumed orally, THC can take as long as 1.5 hours to be absorbed, whereas onset can occur within seconds or minutes when inhaled. Likewise, inhaled THC can remain active for as little as 45 minutes or as long as a couple of hours, while consuming THC orally can lead to up to eight hours of therapeutic or recreational effects. Method of administration can also create qualitatively different experiences, with many patients reporting more intense reactions—both positive and negative—to edibles and oils than to inhaled products.
It is important to note that THC therapeutics rarely contain only THC, but include CBD and other cannabinoids as well. The ratio of THC and other cannabinoids can drastically alter the patient’s experience of relief or of side effects. This is a critical area for patients to consider, as the side effects of THC can be significant and include suppression of executive functions, restlessness, fatigue, anxiety, mood disturbances, paranoia, delusions, and hallucinations. In some cases, avoiding side effects will simply be a matter of finding the right formulation. However, some patients cannot tolerate any meaningful amount of THC due to unpleasant reactions.
Some populations are particularly vulnerable to negative and even dangerous effects. Consistent THC consumption in adolescence has been found to have detrimental impacts on the developing brain, and even isolated use may trigger the onset of psychosis in individuals who are predisposed. Likewise, patients with mental health disorders—including depression, anxiety, bipolar disorder, and schizophrenia—may experience aggravation of symptoms from both short and long-term use. Meanwhile, patients with executive functioning disorders like ADHD may find that their symptoms appear to improve during therapy, only to significantly worsen upon cessation of treatment.
Additionally, while THC is often heralded as a safer alternative to opioid painkillers, recent research suggests that, unlike CBD, THC may increase relapse risk in patients with existing opioid addictions. This is because THC weakly increases the sensitivity of the body’s sigma and mu opioid receptors, a property which it shares with opiate-class drugs. Increasing the sensitivity of the receptors causes them to have a larger physiological effect if they are subsequently activated, enhancing the euphoria, analgesia, anxiolysis, and sedation caused by opioids. In other words, THC potentiates opiate-class drugs. At the same time, this potentiating ability presents possibilities for safer opioid administration in some patients, as THC could be co-administered with opiates so as to keep absolute dosages of the opiate medications low. Furthermore, THC may help minimize withdrawal symptoms in long-term opioid users who are decreasing or eliminating opioid use.
A more pressing concern for many is the addictive potential of THC itself. While it does not carry a risk of physical dependence, some users—including those who initially used THC therapeutically—lose control of their consumption and continue to use despite negative consequences. Additionally, the psychoactive effects of THC can cause both long and short-term cognitive disturbances and behavioral changes that interfere with everyday function and potentially damage emotional, physical, social, and professional well-being.
CBD as a Safe, Multifunctional Treatment Option
CBD shares its origin with THC and has a broad spectrum of therapeutic applications, but does not have any recreational value or addictive potential. Significantly, while CBD targets many of the same endocannabinoid pathways as THC, it does not cause euphoria, disordered thinking, psychosis, or intoxication of any kind. Because CBD lacks these effects, many patients find it to be a better fit for their lifestyle and therapeutic needs compared to THC-based therapeutics; although CBD-based therapeutics also have a very small amount of THC, that THC is typically a leftover from the CBD’s source and is rarely present in concentrations detectable by patients. Given the current evidence, CBD’s safety profile is largely superior to THC, causing minor side effects, like somnolence and fatigue, only with comparatively large doses. As such, CBD is preferred by may patients, is more suitable for long-term and frequent use, does not typically interfere with functionality, and does not carry significant risks for any particular population. Additionally, CBD has a number of applications that go beyond those of THC.
CBD is an effective analgesic when used in conjunction with THC, but can also be used alone for both acute and chronic pain. Interestingly, CBD has been found to prevent pain from spreading from its originating location, a feature that is particularly vital for patients with neuropathic and arthritic pain. Additionally, CBD may lead to a weaker interaction between pain and mood, allowing patients to tolerate the pain with less distress. This capability is likely linked to the ability of CBD to decrease anxiety. Notably, CBD is far more predictable in its anxiolytic effects than THC, which can sometimes cause patients to become paradoxically anxious. CBD’s rate of paradoxical reactions is much lower, making it a safer option for many patients.
Research indicates that CBD may be particularly effective in reducing conditioned anxiety such as in complex psychological trauma or post-traumatic stress disorder (PTSD). More specifically, research suggests that CBD may help patients diminish and better cope with traumatic memories and triggers. In one experiment, mice were administered a mild shock alongside a common environmental noise which they would not find frightening. After several rounds of the shock being paired with the noise, the mice exhibited a fearful response when they heard the noise, even when there was no shock. Next, researchers administered CBD to a group of the mice and played the noise again. 50% of the treatment group exhibited the fear response when they heard the noise, in contrast to 80% of the control group. Impressively, the researchers then demonstrated that CBD enabled the mice to disassociate the memory of being shocked with the noise more rapidly; with repeated exposure to the noise without any concomitant shock, the mice in the treatment group exhibited 10% fewer fear responses after each time they heard the noise.
This extinguishing response is doubtlessly a result of CBD’s ability to affect neuronal energy utilization, a feature which researchers have linked to its potential as an antiepileptic. According to a 2018 meta-analysis of 36 studies on the use of CBD in the treatment of epilepsy, more than 44% of patients were capable of reducing their frequency of seizures by 50% or more with CBD therapy. Furthermore, 8.5% of patients were able to become seizure-free using CBD therapy in isolation, and 55.8% of patients experienced an improved quality of life when on CBD treatment, meaning that its utility as an antiepileptic was superior to other drugs indicated for treatment-resistant epilepsy. Patients whose epilepsy was a result of Dravet syndrome appeared to benefit even more, with 89.3% reporting improved appetite, mood, and sleep quality. These results were preserved among the studies examined by the meta-analysis, meaning that the case for using CBD to treat epilepsy is very strong.
Significantly, while CBD, like THC, may help reduce reliance on opioid painkillers, it may also be safer for people who are currently addicted to opioids. In fact, CBD could be used as addiction treatment; CBD causes a different sensitization response of the opioid receptors, indicating that it would be a more useful tool in helping patients to lower their dose of opiates. CBD may also help to reduce drug-seeking behavior and cravings and could be effective in reducing the discomfort of withdrawal from alcohol and opioids. Importantly, CBD’s ability to affect cravings indicates that it can have a beneficial effect on the brain’s dopamine system, a property which has led researchers to hypothesize that it may be helpful for disorders like schizophrenia. This stands in sharp contrast to THC, which is associated with earlier onset of schizophrenia and greater severity of symptoms.
CBD is typically consumed as a pill, an oral spray, a liquid, or within a food product. Most manufacturers of high-quality CBD therapeutics, like Charlotte’s Web, offer CBD in oil format because it is easy to dose and provides a reliable 8-hour duration per dose. This long-lasting effect is critical for many patients who use CBD to reduce the symptoms of chronic disorders such as epilepsy.
Integrating Cannabinoids in Treatment
While CBD appears to be the more clinically promising cannabinoid when compared to THC for many conditions, many questions remain regarding their separate or simultaneous usage. The majority of the available evidence suggests that CBD is safe for children, but in-depth investigations have not yet been performed. THC, in comparison, has no recognized medical use for children and there is evidence that exposure negatively impacts the developing brain, particularly long-term exposure. Furthermore, researchers have yet to characterize the residual social stigma which cannabinoid therapeutics may face in less progressive regions. Importantly, this social stigma is worsened by criminalization of therapeutic THC in some areas. CBD, on the other hand, does not suffer from the same legal prohibitions.
As our understanding of medicinal cannabinoid use grows, the medical community will undoubtedly expand and refine the therapeutic roles of CBD and THC. In the meantime, however, there is undeniable evidence of efficacy for a number of health conditions. Patients who want to take advantage of these therapies should speak with their medical providers to formulate an appropriate treatment plan and seek out high-quality therapeutics to optimize outcomes.
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