Marijuana as Medicine
by Dr. John McPartland
by Jorge Cervantes
Cannabis (marijuana, hashish) has long been used for recreational and medicinal purposes – for 10,000 years or more. Its medical indications are manifold, including glaucoma, muscle spasticity (e.g., multiple sclerosis), movement disorders (e.g., Huntington’s disease), and a variety of pain syndromes. Marijuana reduces nausea and vomiting and enhances appetite, so it helps people with AIDS and opposes the side effects of cancer chemotherapy. Research shows it can prevent the death of injured neurons. And everyone knows it alleviates anxiety and depression.
Despite marijuana’s unambigious medical benefits, the USA Drug Enforcement Administration (DEA) classifies marijuana as a prohibited Schedule 1 drug (“no currently accepted medical use”). However, tetrahydrocannabinol (THC), the primary active ingredient in marijuana, is classified as a synthetic Schedule III drug (dronabinol, Marinol). The DEA’s hypocritical Classification is rejected by many Americans. More than a dozen states in the USA allow patients to possess marijuana for medical use, contingent upon a physician’s recommendation, but possession remains illegal under Federal law.
Because marijuana remains illegal under the Federal law, its source remains the black market. Patients must obtain their medicine from unregulated producers. You, dear reader, may be one such unregulated producer. Patients depend upon your ethics and expertise t supply them with high-quality medicine, free from contaminants. Jorge and I reckon that dishonorable laws create honor among outlaws, so we entreat all growers to supply only the best organically grown marijuana. The methods for cultivating pharmaceutical-grade herb are outlined in this book. Grow the healthiest plants possible by paying careful attention to the basics: light, nutrients, water, and air. Everything must be in balance, especially nutrients. If you get the balance right, you won’t need to read the chapters on insect and mold control. The most common contaminants of marijuana are mold or pesticides. Optimal cultivation eliminates the possibility of these contaminants.
Of course, optimal cultivation may sometimes elude even the best grower. This book details the use of natural pesticides such as oils and soaps. Better yet, this book promotes the use of biocontrols – commercially available organisms that combat pests and diseases (ladybugs versus aphids being a classic example). Despite all this great information, we still preach the bottom line: “An ounce of prevention is worth a pound of cure.” Even “natural” chemicals may cause problems in some people. The latest edition of O’Shaughnessy’s details the case of a woman who fell ill while manicuring marijuana that had been sprayed with abamectin. Abamectin is a natural compound produced by a soil bacterium. It is approved for use in organic gardens, but, nevertheless, it nearly killed the woman. Grow well and avoid chemicals.
So how does marijuana work as medicine? The question is a proverbial onion, with many layers to peel before we get to the core. The first layer is the medicine’s herbal essence, which is at odds with current medical science. The DEA and FDA criticize the use of herbs as medicines, saying plants contain a variable mix of compounds and cannot provide a precisely defined drug effect. According to the pharmaceutical industry, medicines are synthetic, single-ingredient “silver bullets” that focus upon solitary metabolic pathways in our physiological systems. Herbalists, on the other hand, applaud the polypharmacy of herbal remedies and claim two advantages over singe-ingredient drugs: 1. The many constituents in herbs may work by multiple mechanisms to improve therapeutic activity in a cumulative or synergistic manner. 2. Herbs may also contain compounds that mitigate the side effects of their predominant active ingredients.
Thus, marijuana has been characterized as a “synergistic shotgun” in contrast with synthetic, single-ingredient “silver bullets”. The many ingredients in marijuana modulate our health via several metabolic pathways, gently nudging our system towards homeostasis. This kind of multitasking makes marijuana impossible to evaluate, according to the pharmaceutical industry. But multitasking avoids the unbalanced distortion of solitary metabolic pathways, as produced by synthetic, single-ingredient silver bulets such as Vioxx.
First and foremost in marijuana’s list of ingredients is THC. Tetrahydrocannabinol (THC) is a “new” molecue, produced by cannabis, which evolved within the past 34 million years. Many botanists speculate that THC initially evolved as a toxin to deter herbivores. But this evolutionary strategy was diverted when THC became attractive to humans – the “botany of desire” described by Michael Pollan. THC works in humans by mimicking an endogenous compound that our own bodies make, called anandamide. THC binds to anandamide’s receptors, called cannabinoid (CB) receptors.Research indicates that CB receptors originally evolved in primitive organisms about 600 million years ago! However, as with all chicken-and-egg-questions, the story of CB receptors and cannabis began long before the current pair of protagonists appeared in evolutionary time. It is probable that both CB receptors and cannabis had evolutionary predecessors. They may date to “deep time”, before plants and animals diverged in the primordial soup. Over many eons, CB receptors may have become “vestigial”, analogous to an appendix, only to be reactivated when Homo sapiens discovered cannabis. Humans have interacted and coevolved with cannabis for millennia, creating a complex heterogenous medicine by selecting plants that provide maximal benefits and minimal side effects. The success of 10,000 or more years of human refinement with this botanical medication will be difficult to replicate in modern laboratories. This deconstruction of pharmacological theory is radical, and may herald the reintroduction of herbal medicines into modern medical pharmacopeias, with marijuana leading the way.
When THC or anandamide activate CB receptors, the Cb receptors activate G-proteins. G-proteins are microscopic messengers that migrate around around cells and modulate a variety of ion channels and enzymes. Cannabinoid receptors associate with different subtypes of G-proteins, such as Gi and Gs subtypes. The “i” and “s” abbreviate “inhibitor” and “stimulator”, which describe the opposite effects these G-proteins have on their targets. Research has shown that different cannabinoids preferentially activate different subtypes of G-proteins. This may explain why different strains of marijuana produce different highs. For example, Afghani plants produce a lt of cannabidiol (CBD), and perhaps CBD preferentially activates Gi and causes an inhibitory, stony, narcotic-like effect. Whereas plants from Thailand contain tetrahydrocannabivarin (THCV, a propyl analogue of THC) that might preferentially activate Gs and cause that speedy, buzzy, Thai high.
Thanks to its mix of ingredients, marijuana causes fewer psychological side effects (such as anxiety and panic reactions) than pure, synthetic THC (Marinol). Critical trials have shown that CBD reduces the anxiety provoked by THC, and CBD demonstrates antipsychotic effects. Anxiety from THC may also be alleviated by terpenoids present in marijuana. Many terpenoids are volatile and possess sedative properties when inhaled, including limonene, linalool, citronellol, and terpineol. Terpenoids may also mitigate memory loss cause by pure THC. Limonene, terpinene, carvacrol, and pulegone increase brain acetylcholine activity. This mechanism is shared by tacrine, a drug used for the treatment of Alzheimer’s disease. Terpenoids act on other receptors and neurotransmitters. Some terpenoids act as serotonin uptake inhibitors (as does Prozac), and augment the neurotransmitter GABA (as does Valium). Terpenoids produce anti-inflammatory effects in the respiratory tract. Their presence in marijuana smoke may explain why inhaling marijuana smoke causes less airway irritation and inflammation than inhaling pure THC. Limonene blocks the carcinogenesis induced by “tar” generated from combustion of herb. Limonene is currently undergoing tests for the treatment of several types of cancer. Terpenoids rock.
Dr. Ethan Russo described “endocannabinoid deficiency syndrome”, and suggested that the administration of THC and CBD corrected for deficiencies of either anadamiide or CB receptors. The Administration of THC and CBD corrected for deficiencies of either anandamide or CB receptors. The administrations of THC and CBD seems to kick-start our endocannabinoid system. For example, THC stimulates the release of anandamide, and CBD inhibits the breakdown of anandamide. One study has shown that acute administration f THC may increase the density f CB receptors in the central nervous system. Tolerance and addiction to marijuana is uncommon, in part, because THC is a “partial agonist”. Agonists are compounds that stimulate receptors. Perhaps the best medicines are partial agonists – they steer us away from disease, but our innate healing mechanisms are still required to restore us to complete health. We recall the sheep farmer analogy: when the farmer finds a sheep on the wrong side of the fence, the farmer corrects the situation by pacing the sheep on the other side of the fence, not by carrying the sheep over the fence and all the way to the center of the pasture.
In conclusion, marijuana as medicine is becoming accepted around the world, even among scientists and physicians. Professor John Graham was not far off when he predicted in 1976, “The drug has been frowned upon, officially banned, but the interest of the medical profession is slowly reviving. It is not impossible that a limited but a respectable niche will be established for it in therapeutics by the end of the century”.