The cannabinoids from the cannabis plant work in specific ways in the human body. They target cannabinoid receptors of the endocannabinoid system, often working to achieve homeostasis.
Homeostasis is defined as the tendency towards a relatively stable equilibrium between interdependent elements, especially as maintained by physiological processes. Simply put, homeostasis is a state of biological balance within the body. External stressors such as heat and cold, and internal changes such as blood pressure and pH, all trigger physiological cascades within the body that bring it back into balance. These processes are happening all the time, and are vital to the survival of the organism.
CANNABIS AND HOMEOSTASIS
Interestingly, chemicals derived from the cannabis plant have been shown to greatly influence homeostasis within the body. They have the ability to both reduce and enhance the activity of certain systems, ultimately acting as biological regulators. Cannabinoids achieve these effects in part by acting upon the endocannabinoid system (ECS), a system comprised of enzymes, signalling lipids, and G-protein coupled receptors known as the CB1 and CB2 receptors.
Cannabinoids interact with these receptors due to their structural similarity with molecules created within the body known as endocannabinoids, chemicals that also play a key role in homeostasis.
A 2008 paper published within the journal Endocrine, Metabolic & Immune Disorders Drug Targets explains the important role of the ECS in homeostasis, stating its involvement in neuroprotection and neural plasticity, immunity and inflammation, apoptosis and carcinogenesis, pain and emotional memory, and hunger, feeding, and metabolism.
Various physiological systems work in concert to help the body achieve homeostasis. The hypothalamus, a gland located within the brain, is responsible for maintaining this balance. This gland links the endocrine system and nervous systems, and produces releasing and inhibiting hormones that lead to hormonal cascades throughout the body.
The ECS is present within the hypothalamus, where it plays a regulatory role in maintaining homeostasis, helping to modulate food intake and energy metabolism.
Homeostasis is achieved via both negative and positive feedback loops, with negative feedback loops being the more common response. Negative feedback loops are a regulatory process in which a stimulus catalyses an opposite output in order to maintain a specific state. A thermostat is a prime example of this, being a device that automatically changes the temperature (response) when it reaches a certain point (stimulus).
Negative feedback loops are comprised of 4 main components. The first being a stimulus, the second being a sensor, the third being a control centre, and the fourth being an effector. Negative feedback loops are involved in homeostasis when it comes to temperature regulation, blood pressure, thyroid regulation, and blood sugar regulation.
Let’s use temperature regulation as an example. Negative feedback loops strive to keep our bodies at a constant temperature of 37°C. A potential factor that causes body temperature to rise could be the external temperature (stimulus); the body detects this stimulus via specialised nerve cells that detect temperature changes, known as thermoreceptors (sensor). Thermoreceptors then send a signal to the brain/hypothalamus (control centre), which then dilates blood vessels and initiates sweating (response). This process continues until homeostasis is achieved.
Positive feedback loops are different in that they maintain the direction of the stimulus and may even work to accelerate it. An example of this is the activation of clotting factor during blood clotting or coagulation. Another example is uterine contractions during birth.
HOMEOSTASIS AND DISEASE
A 2016 paper published within the journal Cell states that changes in human ecology such as diet, physical activity, population density, and microbial exposure have dramatically changed the types of human diseases of the last century. These modern diseases involve two main features: disruption of homeostasis and chronic inflammation.
Homeostatic systems can have a fixed point or multiple adjustable set points. Homeostatic diseases can arise when a system becomes stuck in an alternative stable state. Some diseases that stem from homeostatic disruption include dyslipidemia, diabetes, obesity, high blood pressure, arthritis, osteoporosis, thyroid disorders, and endocrine disorders.
ENDOCANNABINOID SYSTEM OF THE SKIN
One area in which the ECS is thought to assist in homeostasis is the skin. Various diseases and conditions of the skin such as acne, seborrhea, allergic dermatitis, itch and pain, psoriasis, hair growth disorders, systemic sclerosis, and cancer may have roots in endocannabinoid system imbalance. Therefore, cannabinoid receptors may be therapeutic targets in treating these conditions.
A 2009 paper published within the journal Trends In Pharmacological Sciences states that the endocannabinoid system in the skin is involved in various biological processes such as proliferation, growth, differentiation, apoptosis, and hormone production.
Another paper, published within the journal ACS Chemical Neuroscience, describes how cannabinoids can influence skin homeostasis to potentially treat multiple conditions. CB1 activation via cannabinoids is associated with the suppression of two types of keratin—fibrous structural proteins that help comprise the skin. This indicates that cannabinoids may help treat psoriasis, a condition in which these types of keratin are upregulated.
The authors also state that cannabinoids have been shown to modulate tumorigenesis and tumour progression in nonmelanoma skin tumours, signifying potential in treating this type of cancer.
APPETITE, WEIGHT, AND OBESITY
Cannabis has appetite-stimulating properties, a quality well known amongst those who smoke the herb. This sensation has been dubbed “the munchies” due to the ravenous hunger it brings about. Cannabis achieves this effect by activating the ECS. Evidence has emerged that suggests the endocannabinoid system is involved in the regulation of appetite, eating behaviour, and body weight.
A paper published within the journal Endocrine, Metabolic & Immune Disorders Drug Targets states that the principle functional role of CB1-mediated effects of endocannabinoids is reorienting energy balance towards energy storage, such as fat deposits. This raises the possibility of utilising cannabinoids as therapeutic chemicals to treat detrimental weight loss. However, cannabinoids may also serve to treat cases of excess weight and obesity due to their influence on homeostasis.
The ECS has been found to control food intake via the hypothalamus and the limbic system. The ECS within the hypothalamus induces enhanced appetite. This system can also increase the motivation for eating due to interactions with reward mechanisms.
CB1 receptors have been shown to modulate metabolism, displaying bodyweight reduction and improvements in lipid profiles within rodent models.
Cancer is caused by the uncontrolled production of cells, with these cells often spreading to other tissues. This process is known as metastasis, a dangerous state that can disrupt organ function and homeostasis.
Precancerous cells are usually dispatched of via a process known as apoptosis. Apoptosis is the controlled death of a cell, and maintains cellular balance within the body. Cancerous cells manage to evade apoptosis and continue to divide.
It has been found that cannabinoids regulate key cell signalling pathways involved in cell survival and metastasis. Cannabinoids such as CBD have been found to induce apoptosis in cancer cell lines, suggesting potential as a future therapeutic for cancer treatment.
One way in which cannabinoids can induce apoptosis is via the mitochondria. Project CBD states that cannabinoids can work in a tri-modular fashion to achieve homeostasis. Cannabinoids can trigger a positive feedback loop within cancer cells, leading to their demise, and thus maintaining homeostasis.
Cannabinoid receptors exist on the cell membrane of some cancer cells. When THC activates the CB1 receptor, of which it is a perfect fit, the cell generates a chemical called ceramide, which induces apoptosis “upstream” of the mitochondria.
The mitochondria serves as the powerhouse of the cell, converting energy sources into ATP. When it’s function is disrupted, the energy supply to the cell is closed off. Cytochrome C and reactive oxygen species are then released into the cytosol, resulting in cell death. Ceramide also works to disrupt calcium metabolism in the mitochondria, another contributing factor to cell death.
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