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When the question “Which cannabinoid is responsible for the marijuana effect?” is asked most users rush to answer that Delta 9 THC is the molecule responsible. In fact, THC has gained fame for being the most psychoactive component of all the cannabinoids but it alone does not determine how any batch of marijuana will affect the user even if we refer only to the pharmacological effect of the cannabis plant. Today we know that the answer to the question is more complex than previously thought.
The flowers of the female Cannabis sativa plant is what we refer to as marijuana. All marijuana varieties produce male and female stock, that is to say, it is a dioecious plant. The female plants produce flowers and a sticky resin which contains more than 90 different cannabinoids; substances produced exclusively by plants of this species. The most known cannabinoids are THC 9, THC 8, Cannabinol or CBN, THCV or Tetrahydrocannabivarin, Cannabichromene or CBC and CBD or Cannabidiol. In addition to cannabinoids, cannabis resin also produces terpenes, which are also present in most fruit trees, aromatic plants and medicinal herbs. Terpenes are the basis for the essential oils of these plants. Terpenes not only define the flavor and aroma of the flower but also influence how the brain absorbs the cannabinoids.
In 1965 Dr. Raphael Mechoulam of the Hebrew University of Jerusalem isolated Delta 9 THC opening up possibilities for new ways of understanding not only the effect of the molecule in the human body but its interaction with the other cannabinoids as well. During the 1970s, many researchers started to work with (the) THC and other cannabinoids in search of answers about its form and action and their medicinal and psychoactive effects. Throughout this time the Pfizer lab developed a synthetic analgesic analogous to THC. The synthetic THC was about 100 times more potent, but the project was abandoned because the psychoactive effects were too strong.
Strong psychoactive effects of THC observed during clinical studies using isolated THC between 1970 and 1980 indicated that the medicinal use of fresh cannabis plants was more effective for the treatment of chronic pain, nausea and other symptoms and ailments for which cannabis is used as a treatment. The use of isolated THC causes great difficulty controlling its psychoactive effects, which can be too intense, and fresh plants showed greater efficacy as medicine. This is somewhat problematic for researchers who wish to record the effects of specific chemicals in isolation. Currently it is known that a balanced THC and CBD dosage is much more effective in treating chronic pain and other symptoms than isolated THC. While THC can cause excessive euphoria and other side-effects such as tachycardia or anxiety, CBD moderates these effects and in so doing enhances the beneficial effects of the cannabis plant.
During the first half of the 1970s studies began to emerge about other compounds of cannabis sativa especially CBD. Researchers who tested the CBD as an antibiotic had greater control in patients with movement disorders such as epilepsy, multiple sclerosis and Huntington’s disease. After the discovery of the anti-inflammatory and antibiotic properties of CBD a number of new studies and applications for medicinal cannabis began. Science now recognizes the medicinal properties of both the THC and CBD compounds of cannabis.
Until recently, it was thought that the CBD and other compounds interacted with the THC affecting the way it was received by the human body. It is known that THC is activated through a reciever in the brain. This receptor, called CB1, has the function of enabling the molecule anandamide which is produced naturally in the human brain. The anandamide was discovered in 1992, and once again surprised the scientists who now had to accept the fact that the human brain produces a molecule identical to THC. This THC-identical molecule fulfills vital functions to ensure human survival.
In 2005 researchers discovered a receptor in the human brain, called CB2, which is responsible for enabling the CBD to affect the human body. Today we know that the CBD is a highly effective medicine and is responsible for appetite stimulation, controlling nausea and vomiting, causing muscle relaxation and drowsiness, anxiety control and it has antibiotic effects as well. Some studies also indicate that CBD aids in the treatment of some types of cancer and autoimmune diseases, such as Alzheimer’s and arthritis.
Researcher Chris Conrad compares the CBD and THC to two nurses; both extremely careful and professional, but with different functions, temperaments, and personalities. Each cannabinoid operates in its individual field of care. THC elevates the mood of the patient. CBD works in specific areas, while keeping the THC under control. In fact, we know that throughout the history of mankind using cannabis, THC and CBD’s existence was known about. Some varieties of marijuana leave the user more euphoric, energetic, and provide a more psychedelic journey, typically occurring in cannabis plants originating from Thailand, Laos, and other equatorial regions. Other types of cannabis are more effective in relaxing the mind and body. Some cannabis varieties alleviate pain and increase appetite, typical effects of cannabis originating in Afghanistan, India, and nearby regions. For millennia humans have selected varieties of marijuana according to their effects and other natural attributes: cannabis plants are chosen for their size and structure, their resistance to pests and diseases, the shape of the flowers, the aroma and flavor of the resin, and of course, for their medicinal and psychoactive effects. Since the discovery of THC, CBD and other cannabinoids became a more significant factor when trying to choose which strains to cultivate and breed with to create hybrid strains.
In recent decades researchers tried selecting plants that possessed higher levels of THC to provide the market with more plants rich in psychoactive substance. However, THC alone in high concentrations can cause undesirable adverse effects. Strains with high value of CBD have previously been ignored by the seed market; they considered the sedative effects less sought-after by consumers. This has changed in recent years, with new discoveries about the medicinal applications of the CBD and medicinal importance and its role as a modulator of the side effects of THC.
In 2009 the cannabis breeder Shantibaba from Mr. Nice Seed Bank, in partnership with Jaime of Resin Seeds, created CBD Crew – a breeding company focusing on plants with high CBD content and making them commercially available. The first strain of the CBD Crew is named Cannatonic and it possesses equal levels of THC and CBD (levels). Today CBD Crew has 8 strains available for sale with varying levels of CBD between 4% and 10% and THC ranging between 4% and 8%. Six of the strains produce CBD and THC in the ratio 1:1 but the CBD Medi Haze and CBD Mango Haze strains can produce ratios up to double the amount of CBD to THC. The CBD Crew has the support of many physicians, scientists, researchers, and patients whose experience and feedback constantly help with improving strains and choosing which lineages of cannabis plants should be used for the breeding project. See the strains of the CBD Crew available from Seedsman.
When we talk about “the marijuana experience” we must bear in mind that all substances contained in the resin of the female flowers contribute to the exclusive psychoactive experience and medicinal value in each plant. THC and CBD are the most active components but all cannabinoids, along with terpenes, act to modulate the psychoactive experience of the plant and also its medicinal effects. Each plant has a single genetic background that will determine not only its growth pattern or its flowers’ shape, but also psychoactive resin composition in terms of amounts and proportions of each of the cannabinoids and terpenes. Each plant is, therefore, a unique medicine, which can better be used for a specific condition. Not only do the psychoactive effects vary with the ratio of cannabinoids, but as we saw, the medicinal effects also vary from one plant to another. It is therefore very important to know each of the components of cannabis to know exactly where you want to go, be it walking a path to achieve a cure or just to enjoy the pleasure of a good cannabis high.
Brazilian Research and Medicinal Applications for CBD
In 2010 the Brazilian Center for Psychoactive Drug Information (CEBRID), at the Federal University of São Paulo, held the International Symposium “Towards a Brazilian Agency of Medicinal Cannabis”. At the meeting, researchers from different countries and authorities of science, medicine and the Brazilian government discussed the feasibility of regulating medicinal uses of the plant in Brazil (already foreseen in the Law 11.343, which has been around since 2006, but for political reasons yet to be deployed). At this meeting Dr. Antonio Waldo Zuardi presented a history of Brazilian research using CBD which is still the basis for many studies on the subject and which I will summarize below. The presentations of Dr. Zuardi (and everyone else who participated in this Symposium) were published in a book in 2012.
According to Dr. Zuardi the 1970 Brazilian researchers were pioneers in the study of the medicinal potential of CBD. In 1970 researchers, who were led by pharmacologist Elisaldo Carlini, began to discuss among themselves that CBD had pharmacological effects. Studies of different samples of marijuana THC ratios (which had varying amounts of CBD), had very different effects on rats in the laboratory. This made the researchers suspect that the CBD imparted its own effects. So began working with the CBD alone, seeking to better understand its effects. In 1973 the first studies identified sedative and anti-epileptic effects with experimental applications in rats.
In 1974 a study with human volunteers the researchers revealed that those who received doses of THC and CBD combined in equal proportions reported less anxiety and a greater feeling of pleasure than those who received a dose of pure THC, or a combination composed of mainly THC. This study was an attempt to analyze the type of psychoactive experience provided by different combinations of the most potent cannabinoids. In the same study it was found that high doses of THC without the presence of CBD can cause similar symptoms of induced anxiety and psychosis, schizophrenia or trigger frames. These effects disappeared when the THC was used in combination with CBD, which suggests that it is able to keep such effects under control. The study opened the door to the possibility of using CBD for the treatment of anxiety and as an antipsychotic. During another study in 1982, it was confirmed that THC alone acted as a provocateur of anxiety and psychotic symptoms yet while in joint administration with the CBD these effects disappeared. Several subsequent studies comparing the CBD with traditional antipsychotic medicine,such as haloperidol and clozapine, shows that the cannabinoid has a performance similar to so-called atypical antipsychotics. This means CBD does not have the side effect of catatonia which in extreme cases can lead to pharmacological Parkinson’s Disease in patients who ingest antipsychotics frequently. The studies also suggest that the CBD has potential for therapeutic use in mental diseases and could even replace commonly prescribed drugs.
During his presentation at the International Symposium Dr. Zuardi described two unpublished clinical studies that were conducted with a total of four patients. All four patients had been diagnosed with schizophrenia and had symptoms that were resistant to treatment with conventional medication. In one study the CBD compared treatment with placebos (no drug effect, used to test the effectiveness of a remedy), and haloperidol during different periods. Neither the patient nor the assistants who administered the “medicine” knew the content or the dosage – a so-called double-blind trial. The same methodology was applied to three patients comparing placebo, CBD, clozapine, and amissulpride. Both studies conducted by CBD showed results comparable to traditional medication (with fewer side effects) and may be considered a useful option for the treatment of schizophrenia frames.
In a study published during 1979 researchers administered doses of 40, 80 and 160mg of CBD or placebo to volunteers complaining of insomnia. All of the volunteers received the “medicine” 30 minutes prior to falling asleep. The results showed that a significant number of volunteers who had taken 160mg of CBD, slept 7 hours or more. In a later study, volunteers receiving morning doses of placebo or 600/300 mg of CBD had at least 6 hours of sleep during the night. The volunteers who received 300mg or 600mg, had a considerable increase in sleepiness after 1 or 2 hours of ingesting the medicine.
During a more recent study that was conducted in 1993 the effects of CBD with the traditional anxiolytic drugs such as diazepam and ipsapirone were compared in patients with Social Anxiety Disorder which had not been previously treated. The sample came from 2313 university student volunteers who answered a diagnosis questionnaire. The volunteers were put into 2 groups, including 12 students with S.A.D., and 12 healthy, social and economic volunteers with profiles similar to peers in the both groups. Both groups were subjected to specific tests that show that CBD alleviates anxiety in the same way that substances traditionally used for this purpose do.
The conclusion is that all studies to date on the potential use of CBD as medicine suggest that CBD has a sedative, antiepleptic, anxiolytic and antipsychotic behaviors. This leads us to believe that there is still much to be discovered not only about the CBD and its medicinal uses but also on the many other cannabinoids that are still unknown. We are still discovering more about this miracle plant today and there is still much more to learn. CBD has been re-discovered by modern society and it is in the forefront of news about medical cannabis. As a scientist friend of mine told me, “To us science people this plant and this medicine is a novelty. Of course, a novelty with thousands of years of existence, but what a fabulous novelty!”. I can’t wait to see these revelations happen faster!
To learn more:
Grotenhermen, F; Russo, EB. Cannabis and Cannabinoids: pharmacology, toxicology and therapeutic potential. Binghamton, NY; p. 27-36.
Guy GW. Whittle BA; Robson P. Medicinal uses of Cannabis and Cannabinoids. London: Pharmaceutical Press; 2004.