The Cannabis Plant
What Are The Medical Benefits Of CBD?
Another selling point of CBD is its non-psychoactive nature. Hence, it does not induce the “high.” Moreover, it also produces little to no side effects and will not result in dependence. On top of it, science has verified that CBD is full of medicinal properties, making it a promising remedy for different health conditions.
Top 10 Medical Benefits Of CBD
CBD is among the most prevalent active compounds found in cannabis plants – second only to THC. Most of the extracts found in the market today are sourced from hemp due to its exceedingly low 0.3% THC, thus confirming to the Farm Bill.
CBD has many effects on the body. Due to its low affinity towards the CB1 and CB2 receptors, however, CBD is not a cannabinoid receptor agonist like THC. Instead, it is said to be an inverse agonist and inhibitor of these receptors. Moreover, CBD does not activate the endocannabinoid system (ECS), only interacting with it indirectly by enhancing anandamide (AEA) signaling.
Aside from this, the non-psychotropic compound regulates non-endocannabinoid signaling systems, such as adenosine, serotonin, vanilloid, glitazone, and G-protein-coupled receptors. The influence CBD exerts on these target sites determine what upshots is produced.
Ultimately, by exploiting how it affects the body on a molecular level, CBD may be able to provide symptom relief for a range of ailments.
In 2004, a study published in the British Journal of Pharmacology investigated the antihyperalgesic action of CBD using a rat model of acute inflammation. The results suggested that transient receptor potential vanilloid type 1 (TRPV1), which is involved in inflammatory responses and pain detection, may play a role in this mechanism. These findings also indicate that target sites other than the cannabinoid receptors mediate the hyperalgesic effects of CBD. In other words, the ECS may not be responsible for the painkilling abilities of the compound.
A 2008 review further explored the pharmacokinetic profile and action of CBD on pain treatment. The results, published in the Therapeutics and Clinical Risk Management, revealed that aside from being a TRPV1 agonist, CBD may also be a CB1 receptor antagonist and endocannabinoid modulator. It suggests that the interplay between the ECS and non-receptor mechanisms may contribute to the analgesic properties of CBD.
CBD also suppresses the activity of GPR55, a type of G-protein-coupled receptor that is associated with neuropathic and inflammatory pain. Such a conclusion came after analyzing relevant literature related to GPR55 in a study published in Pharmacology & Therapeutics.
An even better understanding of the mode of action of CBD came in 2012. A study published in the Journal of Experimental Medicine aimed to assess the effects of CBD on glycine receptors (GlyRs), which is a crucial target for regulating nociception at the spinal level. After a systemic and intrathecal administration of CBD, there was reduced chronic inflammatory and neuropathic pain in rodents. More importantly, the findings revealed that the analgesia could be due to the α3 GlyRs. It suggests that CBD could be used to treat chronic pain involving GlyR damage.
Among the latest research affirming the pain-relieving properties of CBD is a 2018 study published in Frontiers in Pharmacology. After assessing the medical literature on the cannabinoids and pain, researchers posited that CBD could be a safe and effective analgesic agent, especially for treating chronic pain in adults.
As early as 2000, researchers have already experimentally verified the immunosuppressive and anti-inflammatory action of CBD. This study, published in the Proceedings of the National Academy of Sciences of the United States of America, used murine collagen-induced arthritis (CIA) to validate the powerful anti-arthritic effect of the compound. The data revealed that CBD exerted dose-dependent effects, and was effective when administered orally and intraperitoneally. These findings could be tapped for the future development of therapeutic agents for arthritis.
In 2006, another noteworthy study was published in the same journal. This time, the goal was to explore the mechanism behind the anti-inflammatory activity of CBD using 3H-thymidine incorporated into murine microglial cell lines. Researchers found that CBD was immunosuppressive because it could upregulate endogenous adenosine signaling. Again, this substantiated earlier findings regarding the importance of the non-cannabinoid receptor mechanism of CBD.
Three years later, a study published in the Future Medicinal Chemistry also investigated how CBD exerted anti-inflammatory effects. The data revealed that it does so by inducing cell death, inhibiting cell growth, blocking cytokine production, and activating T-regulatory cells (Tregs). The first two control immune cell population, while the last two regulate the inflammatory and immune response.
In 2013, a review published in Phytotherapy Research reported that CBD could be a potential treatment for inflammatory bowel diseases (IBD). Main, that is due to its influence on extra-cannabinoid system receptor sites, such as peroxisome proliferator-activated receptor-gamma (PPAR-γ).
Given its sebostatic and anti-inflammatory effects on human sebocytes, CBD may also be a promising remedy for acne vulgaris. The researchers came to this assessment after examining the effects on human sebaceous gland function using cultured human sebocytes and skin organ culture. These are the results of a 2014 study published in the Journal of Clinical Investigation.
Meanwhile, a 2016 study published in the European Journal of Pain corroborated the earlier findings regarding the anti-arthritic abilities of CBD using a rat model of arthritis. In particular, the data suggested that topical CBD application could relieve the pain and inflammation induced by arthritis without evident adverse effects.
Finally, in a 2018 study published in the Journal of Pharmacology and Experimental Therapeutics, CBD demonstrated anti-inflammatory properties in an experimental model of allergic contact dermatitis (ACD). Thus, it could be a promising therapeutic agent for ACD.
Even as far back as 1976, there is already evidence supporting the antibacterial activity of CBD. This study, published in the Antonie Van Leeuwenhoek, showed 1-5 mµg/ml of THC and CBD was enough to inhibit the visible growth of for staphylococci and streptococci in broth. Moreover, these two cannabinoids also displayed bactericidal properties.
Recently, a couple of notable studies examined this mechanism in greater detail. The first one, published in the Journal of Natural Products in 2008, tested the ability of CBD and other cannabinoids in addressing antibiotic resistance. The results showed that CBD exhibited powerful antibiotic action against various methicillin-resistant Staphylococcus aureus (MRSA) strains.
As for the second one, published in the Frontiers in Cellular and Infection Microbiology this 2019, data collected indicated that CBD might be a useful adjuvant treatment alongside selected antibiotics to boost antibiotic activity. Researchers reached this conclusion after investigating and substantiating the role of CBD in inhibiting the membrane vesicle (MV) release from Gram-negative bacteria.
The 5-HT1a receptor (or the serotonin-1a receptor) belongs to a subtype of receptors that directly binds with serotonin – a brain chemical involved in the modulation of anxiety, mood, and happiness. The 5-HT1A receptor also plays a crucial role in anxiety disorders. For this reason, several studies suggest that activating this receptor could be useful for the treatment of anxiety and other mood disorders.
In 2005, a study published in the Neurochemical Research examined the biological activity of CBD on human 5-HT1a receptors using cell culture. Researchers discovered that CBD acted as a 5-HT1a receptor agonist by stimulating the [35S]GTPγS binding in the G protein-coupled receptor (GPCR) system and by decreasing cyclic AMP (cAMP) concentration. Like most earlier studies, such findings establish the role of CBD beyond the cannabinoid receptors. More importantly, it became elemental to subsequent research on CBD and mood and anxiety disorders.
In 2011, two studies put the anxiolytic action of CBD to test by investigating the effects of the compound on individuals diagnosed with anxiety.
The first one, published in the Journal of Psychopharmacology, found that CBD reduced anxiety in patients with a generalized social anxiety disorder (SAD). By using functional neuroimaging, researchers were able to attribute this activity to changes in limbic and paralimbic brain areas.
Meanwhile, the second one reported that CBD lessened the anxiety in SAD patients who had never received treatment before. Researchers gathered the data by conducting a simulation public speaking test (SPST), then handing out self-evaluations and performing physiological measures throughout the procedure. Within an hour of CBD administration, those with SAD experienced reduced SPST-induced anxiety.
In a 2015 review published in the Neurotherapeutics, the goal was to determine the potential of CBD as an anxiolytic agent. To do this, researchers evaluated the data from preclinical, human experimental, clinical, and epidemiological studies. The existing evidence attests to the efficacy of the compound in treating multiple anxiety disorders when used in the short-term. However, further studies are required to understand the effects of chronic CBD dosing.
Despite the acknowledged role of CBD in managing anxiety, the mechanism behind its action is still not fully grasped. The need for a more profound exploration of its pharmacological properties drives the more recent studies done in 2017 and 2018.
In 2017, an article presented in Pharmacological Research reported that enhancing the gamma-aminobutyric acid (GABA) receptors may contribute to the anxiolytic effects of the compound. Activating the GABA receptors has been associated with calming and relaxing effects.
Meanwhile, a 2018 review published in the Epidemiology and Psychiatric Sciences posited that aside from 5-HT1A receptor agonism, CBD also eased SAD by altering the cerebral blood flow in specific brain regions. Researchers also emphasized the need for future studies exploring the effects of the compound on neurotransmitter signaling, as well as structural and functional cerebral changes.
One of the goals of the 2014 study published in the CNS and Neurological Disorders Drug Targets was to review the antidepressant-like effects of CBD in animal models. The data revealed that CBD did not activate the cannabinoid receptors CB1 and CB2, but interacted with the 5-HT1a neuro-receptor to exert its promising psychiatric effects. The importance of the findings is that it confirmed the earlier studies done on CBD and mood disorders.
The role of the 5-HT1a receptor received further validation in a 2016 study published in Neuropsychopharmacology. Researchers found that acute and chronic CBD treatment in the olfactory bulbectomy mouse model of depression (OBX) produced fast and sustained antidepressant-like effects. This may be due to the stimulation of both serotonergic and glutamate cortical signaling via the 5-HT1a receptor-mediated activity.
In 2018, a research article published in the Progress in Neuro-Psychopharmacology and Biological Psychiatry aimed to have a better understanding of the mechanisms involved in the antidepressant effects of CBD using the forced swimming test (FST) in mice. Results showed that serotonin levels might influence the antidepressant-like effects in the central nervous system (CNS). It substantiates the participation of the serotonergic systems in depression.
Finally, a 2019 study published in Molecular Neurobiology also found that CBD produced rapid and maintained antidepressant-like effects in male rodents. This time, though, it was attributed not to the 5-HT1a receptor, but the changes in the medial prefrontal cortex (mPFC) and by activating the signaling pathway of the brain-derived neurotrophic factor (BDNF) and its receptor tropomyosin receptor kinase B (TrkB). Still, the results affirmed that CBD could be a potential fast-acting antidepressant drug.
In 2012, a critical review published in the Current Pharmaceutical Design looked into the antipsychotic effects of CBD, as shown in animal models and human subjects. The researchers made numerous favorable discoveries. One, CBD may share a similar pharmacological profile with conventional antipsychotic drugs. Second, in clinical trials, the compound appeared to be a safe and effective treatment for schizophrenia. Lastly, the antipsychotic action of CBD could be useful for preventing and reversing the psychotic-like symptoms caused by high levels of THC. All these suggest that the compound may be a potential therapeutic agent for schizophrenia and psychotic symptoms.
In another review published in the Current Pharmaceutical Design, this time published in 2012, the objective was to determine the mechanisms behind the antipsychotic properties of CBD. The data indicated that this might be due to the neuroprotective and anti-oxidative effects of the cannabinoid, which also helped reduce the hippocampal volume loss associated with THC.
Today, there are several pharmacological options available for schizophrenia and other psychotic disorders, which could fall under “typical” or “atypical” antipsychotics. Unfortunately, the use of such drugs is often accompanied by serious side effects. The pressing need for a safe yet effective alternative became the motivation of this 2018 study published in the American Journal of Psychiatry.
In the randomized, multicenter, double-blind, parallel-group, placebo-controlled trial, schizophrenia patients were given CBD or placebo alongside the existing antipsychotic medication. The data revealed that CBD was well-tolerated and led to lower levels of positive psychotic symptoms. The findings support the claim that the compound could be a novel class of treatment for schizophrenia.
To date, the most recent study is the one published in the Journal of Clinical Medicine this 2019. Two of the goals are to examine the potential of CBD in the treatment of psychotic disorders and substance use disorders (SUDs), and to determine whether a specific group of patients would benefit the most from the compound. The researchers found that CBD may be able to attenuate the positive, negative, and cognitive symptoms of schizophrenia. Moreover, patients with early-onset and acute psychosis appeared to have the most promising improvements. It suggests that the compound is more effective in the earlier stages of psychotic disorders.
In 2018, the US Food and Drug Administration (FDA) approved the use of Epidiolex – a highly purified, pharmaceutical-grade CBD-based oral solution – for treating the seizures associated with Lennox-Gastaut syndrome (LGS) and Dravet syndrome (DS) in patients aged two years or older. These are complex, rare, and severe forms of epilepsy that begin in childhood (for LGS) or infancy (for DS).
Later that year, several studies proceeded to explore in greater detail the efficacy of CBD – and in some cases, Epidiolex – in managing the seizures and symptoms of epilepsy.
In a paper published in the Current Neurology and Neuroscience Reports, the primary goals were to examine the anticonvulsant mechanism action of CBD and to provide an update on the recent randomized controlled trials (RCTs) involving the recently approved Epidiolex. For the first one, the data available hinted at the involvement of TRPV1, GPR55, sodium channels, T-type calcium channels, adenosine receptors, voltage-dependent anion-selective channel protein (VDAC1), and tumor necrosis factor-alpha release. As for the second, evidence showed substantial improvement in seizure frequency. However, further research is needed to fully understand the mechanism, side effect profile, and drug-drug interactions of the compound.
In an open-label add-on prospective study involving 72 children and 60 adults with treatment-resistant epilepsy (TRE), researchers found that daily CBD treatment of 20 to 30 mg/kg/day significantly reduced seizure severity and frequency, as well as lessened other adverse symptoms. The results were published in Epilepsy and Behavior.
Another study, published in the Journal of Neurology, Neurosurgery, and Psychiatry showed that using pharmaceutical-grade CBD as adjuvant treatment in pediatric-onset TRE may lower seizure frequency.
This conclusion is echoed in a systematic review and meta-analysis filed in Drugs. After poring over four trials involving more than 500 patients with LGS and DS, the data revealed that adjunctive CBD greatly reduced the seizure frequency in patients that respond poorly to common anti-epileptic treatment regimens.
The latest boost on the potential of CBD in remedying severe TRE comes from a 2019 study published in Molecules. After reviewing the recent scientific literature and clinical trials regarding the effects of CBD on epilepsy, the results showed that the compound could be a useful therapeutic agent for patients resistant to conventional anticonvulsant medications.
8. Anti-Nausea And Antiemetic
Cancer patients undergoing chemotherapy (chemo) often experience nausea and vomiting. This is also referred to as chemotherapy-induced nausea and vomiting (CINV). Unfortunately, while there are pharmacological options, these may cause unwanted side effects. Also, some individuals do not respond well to such medications. The need for an effective yet safe and tolerable antiemetic drug became the basis of this 2010 study published in the British Journal of Clinical Pharmacology.
This pilot, randomized, double-blind, placebo-controlled clinical trial aimed to assess the tolerability, efficacy, and pharmacokinetics of cannabis-based medicines (CBM). The results showed that when used as an adjunct treatment for standard CINV therapies, CBM was well-tolerated and helped prevent delayed CINV. Do note, however, that the CBM used contained not only CBD but THC as well. Thus, the synergy between the two cannabinoids may play a role in the antiemetic abilities of the products used.
In 2011, researchers took a closer look at how the cannabinoids regulated nausea and vomiting using animal models and experiments. The study, filed in the British Journal of Pharmacology, found that the anti-nausea effects of CBD may be due to the indirect stimulation of somatodendritic 5-HT1A receptors found in the dorsal raphe nucleus (DRN).
This hypothesis is put to the test a year later in the same journal by the same group of researchers. To verify the participation of the 5-HT1A autoreceptors and the ability of CBD to target these receptors, shrew and rats were given an intra-DRN administration of CBD. The results revealed that CBD indeed exerted its antiemetic and anti-nausea effects via the indirect activation of the 5-HT1A receptors.
In 2015, a study published in The Cochrane Database of Systematic Reviews analyzed 23 RCTs to determine the effectiveness and tolerability of CBM for CINV in adult cancer patients. The researchers found enough evidence to conclude that CBM may be a potential treatment of refractory CINV.
As observed, most of the studies involved CBM, which also contained THC. Moreover, apart from the 5-HT1A receptors, the involvement of other target areas has not been explored. Thus, clinical trials examining the efficacy and mechanism of CBD on individuals with CINV are of the essence.
9. Anti-Cancer And Anti-Proliferative
The scientific literature on the effects of CBD – and cannabis in general – on cancer is abundant, with more and more evidence regularly being submitted to different journals across the globe.
Among the earlier explorations is a 2007 study published in Molecular Cancer Therapeutics. The researchers described CBD as a nontoxic agent that could inhibit Id-1 gene expression in metastatic breast cancer cells. It means that the compound may be able to help with the downregulation of the activity of tumor cells.
Four years later, in the same journal, a study assessed the mechanism of CBD on breast cancer cells once more. The experiment revealed that CBD prompted cell death in breast cancer cells by mediating the crosstalk between apoptosis and autophagy.
In 2013, a study published in the British Journal of Clinical Pharmacology reviewed the current data on how CBD modulated different steps of tumorigenesis in various types of cancer. The findings suggested that it may be due to its capacity to target several cellular pathways that are involved in the formation of tumors. Moreover, researchers declared that aside from exerting anti-proliferative and pro-apoptotic effects, CBD may also have anti-migratory, anti-invasive, anti-metastatic, and anti-angiogenic properties. All these purport that CBD may have the ability to inhibit cancer growth and spread.
In 2015, researchers claimed that the multiple actions of CBD on cancer cells could help boost the activity of first-line cancer therapeutic agents used in the treatment of cancer. Such a conclusion came after analyzing the antitumor effects of CBD based on existing literature. The results were published in the Journal of Neuroimmune Pharmacology.
The hypothesis that CBD may be able to enhance the efficacy of cancer treatment was picked up and dissected further in a 2018 study presented in Frontiers in Oncology. After going over the available in vitro and in vivo studies, researchers concluded that cannabinoids like CBD might be used alongside radiotherapy (RT) or smart RT biomaterials. Doing so inspires a synergy between the two, which will then improve the effectiveness of conventional cancer treatments. This combination is especially geared towards pancreatic and lung cancers – which, on top of being among the deadliest, are also in dire need of more effective and accessible therapeutic agents. However, the results could also be extended to other types of cancers, such as prostate, liver, and breast cancers.
In a 2019 study published in the Journal of Pancreatic Cancer, the objective was to examine the potential use of CBD and other compounds in the treatment of pancreatic cancer. After a thorough literature review, the data demonstrated that cannabinoids might be a powerful adjunct for pancreatic cancer treatment.
In two other notable 2019 studies – likely among the most recent, too – the main goal was to determine the potential of CBD in breast cancer therapy.
The first one, published in the International Journal of Molecular Sciences, found that CBD may be more effective at the earlier stages of breast cancer, helping slow down tumor progression.
Meanwhile, in the second study published in the Frontiers in Pharmacology, the researchers posited that the antitumor activity of CBD could be tapped for the future development of breast cancer treatments, benefitting patients who are resistant to standard chemotherapy. Moreover, the findings may also be useful for other types of cancers.
10. Neuroprotective And Antioxidant
As early as 1998, the neuroprotective actions of CBD and other cannabinoids were already put to the test using rat cortical neuron cultures exposed to toxic amounts of glutamate. The data indicated that CBD was more protective against glutamate neurotoxicity than ascorbate or alpha-tocopherol – which are known antioxidants. This compound also curbed hydroperoxide-induced oxidative damage as effectively or better than other antioxidants. All these indicate that CBD may be a promising therapeutic agent for oxidative neurological disorders, such as cerebral ischemia.
In 2004, researchers further explored the neuroprotective effects of CBD – this time on beta-amyloid peptide-induced toxicity in rat PC12 cells. The study, published in the Journal of Neurochemistry, found that CBD demonstrated a mix of neuroprotective, anti-oxidative, and anti-apoptotic effects against beta-amyloid peptide toxicity. Moreover, CBD also prevented the appearance of caspase-3, which may then play a role in this neuroprotection.
A 2010 review published in the Pharmaceuticals examined the potential of CBD in treating ischemic stroke. The evidence revealed that the compound its long-lasting cerebroprotective effect was CB1 receptor-independent, and did not induce tolerance or negative health impacts. The significance of the findings is that it substantiated the earlier claims hinting at the therapeutic benefits of CBD for palliating brain injuries.
Two years later, a study looked into the medicinal applications of the neuroprotective action of CBD by investigating its effects on the immune system in general, and oxidative stress in particular. The data indicated that CBD might directly activate the immune system, which could be useful for treating various conditions – including ischemia-reperfusion injury and Alzheimer’s disease (AD). The results were published in Free Radical Biology and Medicine.
Given the positive effects of CBD use and brain ischemia, it is not farfetched to assume that the cannabinoid may also be beneficial for other brain-related ailments – especially neurodegenerative disorders. This is the basis of the 2013 study published in the British Journal of Pharmacology. In particular, the researchers found CBD to be useful for a variety of acute and chronic neurodegenerative disorders, including neonatal ischemia, Huntington’s disease (HD), Parkinson’s disease (PD), Alzheimer’s disease (AD), and multiple sclerosis (MS), among others.
Aside from this, two notable studies from Frontiers in Pharmacology assessed how the neuroprotective mechanisms of CBD would affect other types of diseases.
The first one, which was published in 2017, delved on psychiatric disorders. The findings revealed that CBD could cause plastic changes in the brain that are critical for neuronal survival in neurodegenerative experimental models. It indicates that the compound may be useful for the treatment of psychiatric or cognitive symptoms associated with neurodegeneration.
As for the second one published in 2018, the focus was on the prevention of movement disorders such as PD and dyskinesia, which are linked to oxidative stress and neurodegeneration. The current evidence suggests that CBD could be a promising treatment or preventive measure for these highly debilitating conditions. Even better, it would not induce adverse effects like conventional pharmacological options.
CBD Is A Promising, Multipurpose Therapeutic Agent
The medical community is a buzz with talk regarding the therapeutic potential of CBD and for a good reason. For one, its healing abilities are far-reaching – from alleviating the simplest ills to the most persistent and lethal of diseases. It is also devoid of the qualities that tend to make patients wary of using THC medicinally – the mind-altering high, onset of adverse effects, and risk of addiction, among others.
Given these, it is easy to say that CBD is as safe as it can possibly be. However, those who plan on medicating with this compound should also be aware of its pitfalls, which mostly revolve around complex federal status and insufficient research.
Since the compound is not FDA-approved and mostly illegal, it is difficult to find CBD-based products that are pure, safe, and potent enough. A workaround is to grow it at home for guaranteed quality. Second, further investigation is required to substantiate the role of CBD as medicines of particular diseases, as well as to understand the effects of its chronic use and drug-drug interactions. Combining these two yields another problem – the difficulty in dosing. As there is no standard way of administering CBD, it may take some trial and error to determine the optimal administration method, dosage, frequency of use, and dosage to reap the most benefits.
One thing remains sure, however. There is more than enough scientific proof to show the pharmacological value of CBD in the medicinal community. For now, as experts continue to investigate the compound, the best approach is to get educated before using it and to consult the help of a healthcare practitioner.