Obesity, characterized by excessive fat accumulation that poses health risks, is a complex, multifactorial condition. The storage of excess fat in adipose tissue initiates an inflammatory process, classifying obesity as a low-grade chronic inflammatory disease. Given its complexity and varied contributing factors-including genetic, biological, psychological, sociocultural, and environmental elements-there is no single, universally effective treatment strategy. Consequently, researchers are continuously exploring new therapeutic alternatives, with herbal medicines, particularly those derived from Cannabis sativa, gaining traction for their potential in treating obesity and its associated comorbidities.
The Rising Tide of Obesity: A Public Health Challenge
Obesity has become a significant public health concern, with prevalence rates increasing across all age groups. Updated data from the World Health Organization (WHO) reveals a rapid increase in obesity worldwide, raising concerns about the global economic impact of the disease. Obesity is not only an inflammatory disease but also a trigger for other comorbidities, highlighting the need for specific treatments.
While lifestyle changes, such as reducing caloric consumption and increasing physical activity, are the first line of treatment, they are often insufficient. The development of obesity depends on a diversity of genetic, biological, psychological, sociocultural, and environmental factors. Therefore, pharmacological therapies and herbal medicines are often explored when lifestyle adjustments are inadequate.
Cannabis sativa and Obesity: A Potential Therapeutic Avenue
The therapeutic benefits of Cannabis sativa extracts and their subspecies have been widely studied. Some components of Cannabis sativa are known to stimulate appetite, whereas others are promising for the treatment of obesity. Some drugs derived from the Cannabis sativa plant, called phytocannabinoids, have been studied as a treatment option for several pathologies. This has led to interest in investigating the role of the endocannabinoid system (ECS) in controlling obesity and associated metabolic syndromes.
Understanding the Endocannabinoid System (ECS)
The ECS is a complex network of receptors, enzymes, and endocannabinoids (naturally produced compounds) that helps regulate a vast array of bodily functions, including mood, appetite, sleep, pain sensation, and immune response.
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The ECS consists of two types of endogenous G protein-coupled cannabinoid receptors (CB1 and CB2) that are located in the mammalian brain and throughout the central and peripheral nervous systems. The EC system represents a major neuromodulatory system involved in the regulation of emotional responses, behavioral reactivity, and social interactions. Pathophysiologic manipulation of the ECS has been exploited as a key tool in the management of severe disease conditions of the central nervous system. For example, in recent years, elements of the ECS and its pathways have been explored as therapeutic measures for mitigating some central nervous system diseases such as Autism Spectrum Disorder (ASD) and epilepsy. The endocannabinoid system is also responsible for the maintenance of energy homeostasis and the regulation of lipid and glucose metabolism. Molecular markers have been identified in the ECS membrane transporters (AM404) that could trigger autistic behavior when the cannabinoid receptors are activated.
THCV: A Unique Cannabinoid
Among the various compounds found in Cannabis sativa, Δ9-tetrahydrocannabivarin (THCV) has garnered attention for its unique properties. THCV is a naturally occurring analog of THC. Unlike THC, which is known for its strong psychoactive effects such as altering thinking and problem-solving, distorting perception, increasing anxiety and sedation, and increasing risk-taking behavior, THCV lacks psychoactive effects unless consumed in excessively high quantities. It also has been shown to reduce anxiety and increase energy and alertness. Furthermore, THCV has been shown to reduce appetite, increase fullness and metabolism, making it a potential candidate for improving disease states that impact weight like obesity and type 2 diabetes.
While THC is a weak partial agonist (stimulator) of both CB1 and CB2 receptors in the brain, THCV acts as an antagonist (reducer) of CB1 receptors and a partial agonist of CB2 receptors. This means that THCV can counteract some of the psychoactive effects of THC, while still engaging with the endocannabinoid system to produce some therapeutic benefits. Research has also found that THCV can activate GPR55 and 5HT1A receptors, which may contribute to its potential antipsychotic and neuroprotective effects, making it a possible treatment option for schizophrenia, Alzheimer’s disease, Parkinson’s disease, and multiple sclerosis. THCV can also act as a neutral antagonist of CB1 receptors, meaning that it does not affect the constitutive or basal activity level of CB1 receptors but can block the activity of other CB1 receptor compounds.
THCV vs. THC: Key Differences
The main advantage of THCV over THC is the lack of psychoactive effects. While THCV and THC share a similar molecular structure, their effects differ significantly. Most individuals know THC for its appetite-stimulating effects, or what many refer to as the “munchies”. On the other hand, THCV has been shown to have an appetite-suppressing effect, making it a potential supportive treatment for weight loss.
How THCV Works: Mechanism of Action
THCV primarily works by antagonizing the CB1 receptor; this compound can, therefore, have anorectic effects, inhibiting appetite, controlling food, and consequently decreasing body weight. Stimulation of CB1 modulates the taste and smell pathways to increase the palatability of food. However, at high dosages, THCV can demonstrate CB1 agonism and partial CB2 agonism. Therefore, even though it is a THC analogue, THCV behaves differently in relation to receptors, which may potentiate (in high doses), or antagonize the psychoactive or nonpsychoactive effects of THC.
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THCV is known to act as a CB1 antagonist and a CB2 partial agonist. As an antagonist, THCV blocks the action of cannabinoids at the CB1 receptor, especially in the central nervous system. This action is crucial because CB1 receptors are widely implicated in appetite regulation and feeding behavior.
The metabolic effect of THCV can be explained by its interaction with the transient receptor potential cation channel subfamily V member 1 (TRPV1), also known as the capsaicin receptor. Unlike THC, THCV is observed to induce a therapeutic metabolic effect by restoring insulin sensitivity in obese mice models and interacting with the TRPV1 channels. THCV has been shown to restore insulin sensitivity in diet-induced obese mice models and reducing obesity by modulating the metabolic processes.
THCV and Weight Loss: Research Findings
THCV has been studied for its potential role in weight loss and metabolic regulation. Research in rodents has shown that THCV can reduce food intake, enhance energy expenditure, and improve insulin sensitivity. A 2016 study found that THCV significantly improved fasting glucose levels and pancreatic beta-cell function in patients with type 2 diabetes, indicating its promise in managing glycemic control.
- Appetite Suppression and Weight Management: By blocking CB1 receptors, THCV may help to reduce appetite, curb cravings, and potentially aid in weight management. This is a stark contrast to THC, which typically stimulates appetite.
- Blood Sugar Regulation and Diabetes: Studies suggest that THCV may help improve glucose metabolism and insulin sensitivity, making it a promising area of research for individuals with type 2 diabetes.
- Metabolic Effects: THCV has been shown to restore insulin sensitivity in diet-induced obese mice models and reducing obesity by modulating the metabolic processes.
Administration of intraperitoneal plant-derived THCV in rodents resulted in weight loss, reduced food intake, reduced body fat content, increased energy expenditure, rapid insulin response to OGTT.
THCV Gummies: A Convenient Consumption Method
THCV can be consumed in various forms including cannabis flower, tinctures, and edibles. THCV gummies are a convenient and popular way to consume THCV. They often offer precise dosing and a discreet method of intake. Tinctures are cannabis-infused alcohol or oils administered orally in small amounts usually using a dropper. Tinctures containing CBD or CBN can contain higher concentrations of THCV.
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Other Potential Therapeutic Applications of THCV
Research has shown that THCV offers a variety of therapeutic applications, making it a promising candidate for the treatment of certain medical conditions. Some of the conditions it has been shown to improve include:
- Alzheimer's Disease, Parkinson’s, and Multiple Sclerosis: THCV has been shown to have neuroprotective properties, making it useful for conditions such as Alzheimer's disease, Parkinson’s disease, and multiple sclerosis. Research has shown in Parkinsin’s disease THCV can help reduce oxidative stress and inflammation while potentially delaying disease progression.
- Anxiety & PTSD: THCV has been found to reduce stress, anxiety, and panic attacks, making it useful for individuals with post-traumatic stress disorder (PTSD).
- Seizure & Epilepsy Treatment: As an anticonvulsant, THCV has demonstrated potential in managing seizures, including those associated with epilepsy.
- Schizophrenia treatment: THCV has been shown to interact with 5HT1A receptors, producing antipsychotic effects that could be beneficial for individuals with schizophrenia.
Potential Side Effects and Drawbacks
While THCV has promising benefits, it also has potential drawbacks. Some users report mild side effects such as:
- Dizziness
- Dry mouth
- Increased heart rate
- Mild anxiety at high doses
Compared to THC, THCV has a lower risk of causing paranoia or excessive sedation, but individual reactions may vary. THCV does not appear to have addictive properties. Unlike THC, which activates CB1 receptors and can lead to dependence in some users, THCV acts as a CB1 antagonist at lower doses.
Additional Cannabis Compounds and Weight Loss
Beyond THCV, several other cannabis strains are notable for their potential in aiding weight loss.
CBD, a major cannabinoid found in cannabis, may contribute to the transformation of white fat into brown fat, which is more metabolically active and burns more calories. CBD also decreased resistin and increased levels of glucose-dependent insulinotropic peptide. CBD enhanced expression of a core set of brown fat-specific marker genes (Ucp1, Cited1, Tmem26, Prdm16, Cidea, Tbx1, Fgf21, and Pgc-1a).
Cautionary Note
It is important to note that Cannabis sativa is not a miracle plant. Despite the medicinal benefits of marijuana, its chronic use has been linked with conditions such as psychotic disorders and cannabis use disorder, while acute consumption is linked to psychotic symptoms, hyperemesis syndrome and anxiety.