Medicinal Marijuana & the Endocannabinoid Receptors: What We Know So Far
The human body contains naturally occurring receptor sites for endocannabinoid compounds, which is what causes our minds and bodies to react to plant-based cannabinoid compounds. These receptors are what make cannabis so effective in terms of its medicinal applications, and the truth is it’s always been this way, as archaeology has confirmed.
Cannabis has been used as a natural, effective, plant-based medicine for at least 7,000 years, which is as far as back as we can determine using historical dating. Use of the plant likely goes back even further than this, but it’s nearly impossible to gauge how far given that researchers are dealing with rapidly decaying archeological records.
Chemical analysis of Egyptian and Peruvian mummy bones and tissues has revealed cannabinoid compounds dating as far back as 2,900 BC. Hieroglyphic evidence of therapeutic administration is consistent with this time-dated analysis.
In 1993, a team of German anthropologists published the results of an analysis of various tissues from 72 Peruvian mummies circa 1,800-500 BC. The bones from 20 of them contained cannabinoids. In addition, an MRI analysis of a 2,500-year-old Mongolian princess mummy revealed she died from breast cancer and was buried with cannabis in her tomb.
The cannabis was recovered and its psychoactive compounds were still active. In fact, the secretory reservoir on the trichomes had fossilized and turned bright red.
Following the Cannabis Trail
Many people believe the cultivation of naturally occurring landrace varieties of cannabis began in the Hindu Kush mountain range in Asia, and moved out via trade routes—southwest into Egypt, east into Mongolia, west into the Mediterranean, and as far north as England and Scandinavia—all by the time of the Roman Empire. A sub-strain called C. Ruderalis, which is self-pollinating and is not photoperiod-sensitive, evolved in southern Russia.
Today, cannabis use is global, and its application in spiritual ceremonies and applications by shaman healers are well-documented. My work focuses on the chemical analysis of landrace varieties from Afghanistan (Hindu Kush), Morocco (Atlas Mountains) and South Africa (Kwanza Zulu). These are all pure, ancient, isolated, unadulterated strains of indicas and sativas. I am using these strains to develop a baseline cannabinoid distribution analysis.
I will use my analysis to compare modern hybrids as they relate to the distribution of different compounds in the landraces, and how they are expressed in modern cross-pollinations to create such varieties as Blue Sky Cotton Candy or Orange Bud. For instance, there may be a way to associate their therapeutic effects with their terpene compounds.
Understanding Receptors CB1 and CB2
As the human race has grown up, cannabis use has grown along with it. Cannabis plants and humans are genetically and biologically compatible due to the receptor sites in the human body. One might make the case that the cannabis plant is genetically one of many ancestors of the human genome.
There are two types of cannabinoid receptors in the human body—cannabinoid receptor type 1 (CB1) and cannabinoid receptor type 2 (CB2)—that sense molecules outside the cell and activate inside signal transduction pathways and cellular responses. As they are coupled with G proteins (guanine nucleotide-binding proteins), they fall into the category of seven-transmembrane receptors, meaning they pass through the cell membrane seven times.
The CB1 receptors are approximately 473 amino acids in size and are located primarily in the central and peripheral nervous systems. They are activated by the endocannabinoid neurotransmitters anandamide and 2-arachidonoylglycerol, and by plant cannabinoids. CB2 is a cannabinoid receptor, approximately 360 amino acids in size, from the cannabinoid receptor family that, in humans, is encoded by the CNR2 gene.
CB1 receptors are primarily located on nerve cells in the brain and spinal cord, but they are also found in some peripheral organs and tissues such as the spleen, white blood cells, endocrine gland and parts of the reproductive, gastrointestinal and urinary tracts.
In the brain, CB1 receptors are abundant in the cerebellum, basal ganglia, hippocampus and dorsal-primary afferent spinal cord regions, which is why cannabinoids influence functions such as memory processing, pain regulation and motor control. In the brain stem, the concentration of cannabinoids is low, which may be why cannabis use is not associated with sudden death due to depressed respiration, as is the case with heroin overdoses.
CB2 receptors are mainly found on white blood cells, in the tonsils and in the spleen, which allows for the blood-borne distribution of compounds to various parts of the body. In the immune system, one important function of the cannabinoid receptors is the regulation of cytokine release.
It is the stimulation of the CB1 receptor that gets people high and leads to things like increased appetite, mood elevation, stimulation of thought and creativity, and enhanced sensory sensitivity and perception. In contrast, these effects are not seen when the CB2 receptor is activated.
Therefore, selective CB2 receptor agonists have become increasingly popular subjects of research for their potential anti-inflammatory and anti-cancer effects. The fact that the CB2 receptor is found on macrophage cells indicates the immune system cells can bring the cannabinoid compound to the site to assist in the fight to kill diseases, reduce inflammation and alleviate pain.
Cannabis…it does a body good!
Endocannabinoid Receptor Related Words To Know
Trichomes - Trichomes are fine outgrowths or appendages on plants with diverse structure and function. Including hairs, glandular hairs, scales and papillae, they are the primary source of cannabinoid and terpene development of the cannabis plant.
Landrace - Landrace is a local and often isolated variety of a domesticated plant species that has developed over time, through adaptation to the natural environment in which it lives.
Indica - Indica is one of the two main subspecies of cannabis, indica tends toward shorter, wider plants with a deeply relaxing and calming effect helpful for treating anxiety, pain and sleeping disorders. Best suited for night use.
Sativa - Sativa is one of the two main subspecies of cannabis, sativa plants are tall and thin with an energetic and uplifting effect helpful for treating emotional imbalance and depression. Best suited for day use.
Cannabinoid - Diverse chemical compounds that act on cannabinoid receptors and repress neurotransmitter release in the brain. The active constituents of cannabis, at least 85 variations have been isolated, including THC and CBD.
THC - The cannabinoid called tetrahydrocannabinol is the primary psychoactive compound of cannabis.
CBD - The cannabinoid called cannabidiol is the secondary constituent compound within cannabis.
Terpene - A large and diverse class of organic compounds produced by a variety of plants that provide aromatic and flavor diversity.
Receptor - A protein molecule that receives chemical signals from outside a cell.
CB1, CB2 - Human body cannabinoid receptor types.
G proteins - Guanine nucleotide-binding proteins.
Guanine - One of the four main nucleobases found in the nucleic acids DNA (deoxyribonucleic acid) and RNA (ribonucleic acid).
Nucleotide - Organic molecules that serve as sub-units of nucleic acids like DNA and RNA.
Cell Membrane - The semi-permeable membrane surrounding the cytoplasm of a cell.
Amino Acids - Biologically important organic compounds containing an amine (-NH2) and a carboxylic acid (-COOH).
Endocannabinoid - Substances produced naturally within human and animal bodies that activate cannabinoid receptors.
Neurotransmitter - Endogenous chemicals that enable neurotransmission (communication) by transmitting signals across a chemical synapse, such as a neuromuscular junction, from one neuron (nerve cell) to another target neuron, muscle cell or gland cell.
Cytokine - Intercellular messengers that play key roles in the regulation of the immune response as the source of soluble regulatory signals that initiate and constrain inflammatory responses to pathogens and injury.