Medical cannabis is defined as the use of synthetic forms of cannabis and cannabinoids for certain diseases as a form of treatment recommended by a doctor. Although there are not enough unbiased scientific studies demonstrating the potential therapeutic value and side effects of cannabis on an evidence-based basis, many scientific and medical institutions support scientific studies on medical cannabis. Therefore we can say that cannabis can be used as a drug. So, what type of drug is cannabis classified as?
Cannabis is not actually classified as a certain type of drug. It exhibits hallucinogenic, stimulant, and narcotic effects together. The narcotic properties of cannabis are used in medicine. Cannabis can be used as a pain-relieving drug. Along with its painkiller feature, cannabis can also help to relieve nausea and vomiting, especially those seen with chemotherapy. Cannabis-derived drugs are started to be used in the last decades. They are also believed to be useful in the treatment of psychiatric diseases.
Use of Cannabis as a Medicinal Drug
Cannabis is an ancient type of drug. Since the first discovery of cannabis, its medical uses have been emphasized and many studies have been conducted on this subject. However, considering the neuropsychiatric side effects and the effects on public health, it is seen that the studies are insufficient. There is evidence of the effects of cannabis on some of the symptoms associated with neurological disorders, such as multiple sclerosis (MS) and chronic pain. MS is a progressive, chronic disease in which there is a demyelinating pathology of the central nervous system.
This disease is characterized by many symptoms such as spasticity, muscle cramps, chronic pain, visual disturbances, tremors, and gastrointestinal system dysfunctions, all of which are considered to be the result of demyelination. Clinical studies have shown that cannabis-based drugs are likely to be effective in relieving some symptoms of MS. It has been reported that cannabis-based drugs subjectively reduce MS symptoms while reducing pain and increasing appetite.
Although cannabis-based drugs such as Nabiximols and THC have improved some of the symptoms of MS, some studies note that cannabis has a negative effect on cognitive and physical functions accompanying alleviation of MS-related symptoms. He reported worse cognitive functions in MS patients who use cannabis compared to MS patients who do not use cannabis. In addition, more psychiatric symptoms were found among cannabis users.
Although research on cannabinoids and pain in cancer patients continues, it has been determined that the administration of single oral doses of THC to patients with cancer pain has an analgesic effect. 10 mg of THC was well tolerated, showed an anxiolytic effect, and was thought to have analgesic potential. However, THC administered at a dose of 20 mg has been reported to cause side effects that prohibit its therapeutic use, including somnolence, dizziness, ataxia, and blurred vision.
Some recent studies have found that combining an oral spray of THC with CBD reduces pain in patients suffering from chronic pain, central neuropathic pain, and pain caused by rheumatoid arthritis. Finally, it showed that cannabinoid drugs are indeed analgesic drugs in acute and chronic pain. There is also low-quality evidence that cannabinoids are associated with the treatment of chemotherapy-induced nausea and vomiting, AIDS-related pain, and improvement of sleep disturbances.
It has been previously stated that especially CB2 receptors are found in the immune system. Based on this information, promising results were obtained in studies on the use of cannabinoids in patients with systemic sclerosis. Systemic sclerosis is a multisystem autoimmune disease characterized by internal organs, skin fibrosis, and vascular damage. It has been reported that heart, lung, and kidney involvement may have a high prevalence leading to increased morbidity and mortality, especially in extensive systemic sclerosis.
Cannabinoids have recently been suggested as a possible new treatment that could limit disease progression. Thanks to the effects of cannabinoids on the immune system, it has been determined that by reducing and balancing many factors that cause autoimmunity, it stops the progression of the disease. Although the psychoactive side effects, addictive effects, and many other psychiatric effects of cannabis limit its medical use, there is research that it can also be used in some psychiatric diseases.
In these studies, post-traumatic stress disorder and social anxiety are the most interesting ones. In a study by experts, they did a brain imaging study on patients who took oral CBD and had social anxiety. A short-term CBD treatment has been reported to cause a reduction in subjective anxiety symptoms and a reduction in limbic and paralimbic brain activity. In another double-blind randomized controlled trial, patients with social anxiety were given CBD or a placebo before a public speaking task. Mood, cognitive and mental distress measures were recorded before and after the task.
It has been reported that the CBD group had lower levels of subjective anxiety during the task, as well as lower cognitive impairment and feelings of distress when compared to placebo and healthy subjects. In post-traumatic stress disorder (PTSD), a reduction in stress and anxiety symptoms has been observed after cannabinoid treatment. In some recent clinical studies; It has been reported to show reduced PTSD symptoms and improved quality of life following treatments with various cannabis-based drugs, including THC, cannabis, and nabilone.
The main reason why some PTSD patients also use cannabis is that these patients are actually self-medicating without realizing it. In a recent clinical trial, a double-blind, randomized study was conducted to compare the efficacy of CBD with the atypical antipsychotic amisulpride in reducing symptoms of schizophrenia. It was found that both cannabidiol and amisulpride led to a significant clinical improvement, but cannabidiol showed a significantly better side-effect profile.
In addition, cannabidiol treatment was accompanied by a significant increase in serum anandamide levels, which was significantly associated with clinical improvement. It has been suggested that the mechanism of increase in anandamide levels may contribute to the antipsychotic effects of cannabidiol and potentially represents a new mechanism for the treatment of schizophrenia. A large randomized double-blind controlled trial was conducted in schizophrenic patients receiving CBD therapy, versus schizophrenic patients receiving placebo alongside ongoing antipsychotic medication.
Patients were evaluated for positive and negative symptoms as well as cognitive function measures before and after 6 weeks of treatment; It is found that after 6 weeks of treatment, the CBD group had fewer positive psychotic symptoms and showed greater clinical improvement. Moreover, CBD was well tolerated and rates of side effects were reported to be similar to placebo.
Psychiatric Disorders and Cannabis as a Drug
An important issue that should not be forgotten when discussing the medical use of cannabis is the high incidence of psychiatric disorders in people who use cannabis. According to a national survey (NDSHS) conducted in Australia in 2004, psychiatric disorders were observed in 11% and 14% of men and women who did not use cannabis, while a mental health disorder was found in 21% and 29% of men and women who were active cannabis users. Eight psychopathological conditions caused by cannabis as the main responsible substance have been reported in DSM-IV-TR.
The cases of cannabis intoxication and withdrawal that occur with cannabis use are generally considered uncontroversial. The issue of marijuana addiction is still controversial. In addition to these direct causes, marijuana is also thought to worsen pre-existing psychiatric disorders (panic, depression, psychosis) or to cause a disease that has not yet emerged. Johns et al. reported that cannabis poisoning lasted longer in people with a diagnosis of schizophrenia or personality disorder.
Although it has been reported that cannabis is used for “self-treatment” in anxiety disorders, there are no studies showing that cannabis can be used as anxiolytic or anxiogenic. All these studies indicate that even if cannabis does not directly cause a psychiatric disorder, it may cause more disorders in some susceptible individuals with a family history or any psychiatric history.
In addition to these caveats, THC content in the genetically modified cannabis plant has increased significantly from 1-5% to 10-15% since the late 1960s. This increase may be caused by the greater effect of cannabis, the more pronounced psychiatric effects, and the increase in cannabis addiction.
Biological Mechanism of Action of Cannabis as a Drug
Today, it is thought that there are 3 groups of cannabinoids. These are natural, endogenous, and synthetic cannabinoids. Since THC is a fat-soluble substance, it easily crosses the blood-brain barrier and causes more psychoactive effects. THC is the most abundant natural cannabinoid in cannabis. Cannabidiol comes second. Cannabidiol, on the other hand, causes anti-inflammatory, analgesic, anxiolytic and anti-seizure effects. The proportion of these cannabinoids can produce a wide variety of effects, as they vary widely among cannabis varieties.
For example; It has been reported that when CBD is applied with THC, it reduces the unwanted effects of THC such as anxiety, fear, and tension. The brain endocannabinoid system generally consists of endogenous cannabinoids, enzymes that synthesize and break them down, and specific cannabinoid receptors. It has CB1 and CB2 cannabinoid receptors. While CB1 receptors are commonly found in many parts of the brain; CB2 is found in peripheral tissues and is thought to be associated with the immune system. THC binds to CB1, but not to CB2.
CB1 receptors are held responsible for many psychoactive effects such as pain, mood elevation, panic reactions, memory, deterioration in time perception, tension, depression, perception disorders, and cognitive functions. Endogenous cannabinoids are anandamide and 2-arachidonoylglycerol. Endogenous cannabinoids have a shorter half-life and less potency compared to THC. Synthetic cannabinoids are cigarettes in the form of a mixture of several different synthetic cannabinoids, which are prepared by mixing with plants called Jamaica or bonsai and are often referred to by these plant names.
Although the mode of action and content of synthetic blood cannabinoids are not known exactly, they pose a greater risk to users than cannabis. Synthetic cannabinoids are thought to stimulate their receptors much more strongly and for a long time. When cannabis is taken orally, it shows less efficacy because it is eliminated in the liver. Its effect starts late, but its effect starts faster when inhaled.
The effect of cannabis taken by inhalation starts within minutes and takes effect after 1.5-2 hours when taken orally. The duration of action of cannabis varies between 2 and 4 hours. The effect of cannabis varies according to the type of use, the dose used, the substances used together, the strength of the components of cannabis, and the past experiences of the person.
Acute and Subacute Effects of Cannabis
Although the effects of cannabis are similar for many people, the effect seen may differ from person to person due to some factors such as the way of use, dose, and type of cannabis, as stated before. Shortly after ingestion, cannabis produces some physiological symptoms such as redness of the eyes, increased heart rate, and muscle relaxation. Later, central nervous system findings such as loss of balance, memory loss, distraction, relaxation, relaxation, cheerful mood, perceptual changes, and uncontrolled laughing appear. Some people may also experience disturbing emotions such as fear, tension, and worry.
The effects of cannabis have been the subject of many studies in the past, and some previous studies have included the subjective experiences of cannabis users. Ludlow, who uses cannabis regularly and in high doses, describes in his book “Hasheesh Eater” how he felt euphoric after using cannabis: “I clapped my hands and shouted with joy… I glowed like a new-born soul. I also experienced a change in the sense of self and a change in the passage of time.”
Some recent studies show that cannabis use impairs cognitive and brain function. In a study, it is examined whether cannabis use affects the relationship between age at onset and cognitive disorders. According to the results obtained, it has been observed that cannabis use in older adults can exacerbate the decline in age-related cognitive functions, adolescent users show more deterioration in executive functions than adults, but the recovery is faster when they quit cannabis.
Another study found that regular use of cannabis was associated with volumes of brain regions associated with learning, reward, and addiction. These pathways have been described in neuropsychiatric theories of addiction, and volume changes have been demonstrated in substance use disorders other than cannabis.
There has been increasing evidence of impairments in various cognitive domains among those who do not use cannabis on a daily basis. However, tolerance to cognitive impairments can develop in those who use cannabis on a daily basis, and cognitive impairment can be observed when cannabis use is suspended.
The acute effects of cannabis on cognition may depend on the THC/CBD ratio, and high CBD concentrations protect against cognitive impairment. It seems that one reason for the different efficacy of cannabis use is the different ratios of THC and CBD in the substance used. Since the forms of cannabis currently dominating the market have very low CBD and high THC content, it is difficult to determine what type of cannabis’ positive or negative effects are due to.
Cannabis has been reported to have acute and transient effects on mood in general. Acute effects; relaxation includes, but is not limited to, a combination of effects reported as euphoria, relaxed inhibitions, and a sense of well-being. Although cannabis reduces anxiety, especially at low doses, it is thought that it may increase the panic-like effect due to the high THC concentration found in cannabis in recent years. It has been reported to increase anxiety when THC alone is administered at high doses, especially under stress conditions.
In contrast, THC administered with CBD provides protection against possible anxiety. Consistent with the notion of the biphasic effect of cannabinoids on anxiety-like behaviors, genetic studies in mice are reported to be associated with influencing the amount of excitatory or inhibitory neurotransmitters in different brain regions. While cannabis use severely impairs attention, it has been found that selective, focused, and divided attention are impaired after cannabis use in healthy individuals.
Among the memory areas affected by acute cannabis use; are spatial working memory, procedural memory, verbal learning, recall, and relational learning. The areas most affected are verbal learning and memory areas. In addition, the use of cannabinoids in many systems of the body creates different effects such as increase and decrease in heart rate, life-threatening heart rhythm disorders, blood pressure changes, heart attack, and shock.
While it can cause cough, shortness of breath, irritation in the throat, lung cancer and failure in the respiratory system; nausea, vomiting, abdominal pain, bleeding, and intestinal perforation in the digestive tract; It can cause musculoskeletal pain and contractions, excessive sweating, decrease in blood sugar, and changes in appetite.
Cannabis as a Drug to Treat Anxiety, PTSD, ADHD, Bipolar Disorder, and Sleep Disorders
Anxiety and related disorders are closely related to cannabis use. Cannabis has a biphasic effect on anxiety. As mentioned before, short-term cannabis use has an anxiety-relieving and sedative effect at low doses, while it can cause fear, anxiety, and panic attacks at high THC concentrations. While the excess THC concentration in the cannabis component causes anxiety, CBD provides protection against anxiety.
While cannabis use, especially for many years, can increase anxiety and even cause panic attacks, it also exacerbates the neuroendocrine response to stress. While individuals with anxiety disorders report high rates of cannabis use, it is difficult to ascertain the extent to which self-medicated cannabis contributes to anxiety disorders.
It is stated that cannabis can reduce the symptoms of the disease in patients with post-traumatic stress disorder. In some female patients diagnosed with PTSD, they report that cannabis shortens the time to fall asleep, increases the duration of sleep, and reduces the frequency of nightmares. According to the data of the Multidisciplinary Association for Psychedelic Studies, which has been operating in the USA since 1986, it aims to obtain approval for the legal use of cannabis in PTSD patients. In this regard, in 2014, a study was approved for the use of herbal cannabis in PTSD patients; The study, which started in 2017, has recently ended and the study is at the stage of publication.
Attention Deficit Hyperactivity Disorder is one of the frequent and important diseases of childhood, which manifests itself with attention deficit or disorganization, concentration disorder, hyperactivity, and impulse control disorder. The prevalence of ADHD is higher than expected, and it is a disorder that can be seen not only in children but also in adults. According to the data from the American Psychiatric Association; It is stated that its prevalence in the world is 5-12% in children and 4.4% in adults.
ADHD patients may use substances for self-medication, especially for symptoms such as impulsivity/irritability and distraction during the diagnosis process. For this purpose, cannabis is among the most frequently used substances; In a study on this subject, it is reported that the use of cannabis is beneficial in the treatment of ADHD patients. It has been reported that cannabis slows down the rapid thought process in ADHD and has fewer side effects than stimulant drugs in treatment.
- Bipolar Disorder
Bipolar disorder is a disorder that includes an elevated mood episode and a depressed mood episode. Patients periodically feel extraordinarily happy, energetic, and talkative. There may be sudden mood swings from time to time, and this is the mania period when the amount of sleep decreases. Also, depressive episodes with symptoms such as depressed mood, not being able to enjoy life, low energy, and thoughts of worthlessness can be seen periodically in these patients.
Looking at the coexistence of substance use disorder and bipolar disorder, there is a particular trend for increased rates of cannabis use and substance use disorder diagnosis in people with bipolar disorder. Also, compared to depressive disorder, individuals with bipolar disorder use cannabis more frequently and in higher amounts. A study based on NESARC data showed an association between substance use disorder and the frequency of bipolar-related symptoms, as well as other substance use comorbidities.
Available data provide evidence that cannabis exacerbates bipolar disorder symptoms. Many studies show that when patients with bipolar disorder are accompanied by a substance use disorder, they generally experience a worse course of illness and are more severely overcome by manic, hypomanic, and depressive episodes. There may be a connection between cannabis use and the duration of the manic state; It is reported that the earlier one starts using cannabis, the more the risk of the bipolar disorder increases, and the use of cannabis increases the risk of developing the disease five times.
There are few studies that show that cannabis use may have benefits for bipolar disorder. In the book titled “Forbidden Medicine”, it is stated that 30-40% of patients with bipolar disorder do not benefit from conventional treatment; It is stated that cannabis may be beneficial in improving symptoms or reducing lithium side effects in these patients.
- Sleeping disorders
Sleep disorders are frequently seen in psychiatry clinics and the rate of accompanying psychiatric diseases is high. There is a belief that cannabis is good for sleep disorders and has fewer side effects compared to medical treatment in regular cannabis users. When synthetic THC was applied in comparison with amitriptyline in a group of patients with sleep disorders diagnosed with fibromyalgia; It was observed that there was an improvement in complaints in both groups.
However, it has been reported that nabilone is more effective on sleep and causes fewer side effects compared to amitriptyline. In contrast, those with cannabis use disorders had a higher rate of sleep disturbances after quitting cannabis. In these patients; Decreased sleep duration, delayed falling asleep and slow-wave sleep are the most common sleep symptoms.
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