While some studies suggest that cannabis can be effective in reducing seizures, new research points out that strong and synthetic forms of the drug have the opposite effect. Researchers suggest that the use of potent cannabinoids has the potential to trigger seizures. Researchers at Tsukuba University in Japan have found that natural tetrahydrocannabinol (THC) – the psychoactive chemical in cannabis – and synthetic cannabinoid JWH-018 cause seizures in mice.
Study leader Olga Malyshevskaya and her colleagues say their findings, published in the Scientific Reports magazine, should serve as a “public warning” to the potential harm caused by high-impact and synthetic cannabis. Cannabis remains the most widely used illicit drug in the United States, while it is increasingly legalized in individual states for medical purposes, recreational purposes, or both.
Although there is increasing research on cannabis use, cannabis use – especially cannabinoid use of cannabinol (CBD) – is increasing in research on the treatment of seizures in epilepsy patients. A recent study by Malyshevskaya and his team suggests that the general use of high potency marijuana (ie, marijuana with high THC) may cause seizures. The study also demonstrated that seizures could be triggered by JWH-018, a man-made cannabinoid, the main component of synthetic cannabis known as “spice.”
Seizure Frequency of Jwh-018 Is Higher
The researchers analyzed the brain activity of male mice after receiving THC or JWH-018 and reached their findings. THC was given to rodents at doses of 10 milligrams per kilogram (equivalent to 0.8 milligrams per kilogram in humans) and JWH-018 was administered at a dose of 2.5 milligrams per kilogram (equivalent to about 0.2 milligrams per kilogram in humans). The team implanted electroencephalography (EEG) and electromyogram electrodes into the brains of mice, allowing them to monitor the electrical activity of any seizure in response to drug compounds. Research suggests that cannabis use may be more harmful to cardiovascular health than smoking.
The movement and behavior of the rodents were also monitored by video recording. The study found that mice had seizures shortly after administration with THC and JWH-018, although the frequency of seizures was significantly higher with JWH-018. Seizure-related brain activity continued 4 hours after each drug administration, team reports, but brain activity returned to normal the next day. Interestingly, the researchers found that pretreatment with AM-251, a compound that binds to the cannabinoid-1-receptor of mice, prevents seizures in response to THC and JWH-018. In this way, the team suggests that in the case of a cannabis overdose, cannabinoid receptor antagonists may be useful for the prevention of seizures.
- The Study Warns of Possible Dangers
According to the researchers, their results provide “strong evidence” that plant-derived and synthetic cannabinoids have the potential to trigger seizures. On the other hand, the authors indicate that “an important source of literature on cannabinoids in animal models is mostly anticonvulsive effects. However, some of them have used EEG recordings to evaluate epileptic events, and many of them have caused electrical or pharmacological seizures, changed the status of signaling pathways and brain before cannabinoid administration.
The team notes that the doses of THC and JWH-018 used in their studies are high and cannot normally represent doses seen in medical or recreational use in humans. “In the future, it would be interesting to test lower doses, which are often used medically or recreationally to determine whether the effect has been lost,” they add. Nevertheless, they believe their findings should be seen as a warning of the potential dangers of cannabinoids, especially synthetic cannabis.
Seizures in Panic Attacks in Cannabis Use
Cannabis is the most frequently used illegal substance. Cannabis use often results in euphoria, sedation, and relaxation. However, cannabis can cause panic attacks, depersonalization, and psychosis as well. Although there is no definite information about the mechanisms by which cannabis causes panic attacks, it is stated that tetrahydrocannabinol (THC), its active metabolite, is responsible for psychiatric symptoms. It has been reported that THC affects neurotransmitter levels and benzodiazepine receptors in the brain. If the panic attack, which occurs for the first time during cannabis use, continues in the period when cannabis is not used, it can be diagnosed as panic disorder.
Considering that panic attacks occur mostly in inexperienced users and with the first use of cannabis, cannabis use in people may not necessarily cause panic attacks. It is seen that it is necessary to question the history of cannabis use. In panic disorder, the main feature of the panic attack is that it can be expected even if there is no triggering situational event or a chemical substance. However, it has been reported that panic attacks may be triggered by chemicals such as lactate, yohimbine, caffeine, alcohol, nicotine, and cocaine. There are some reports in the literature that cannabis use can cause panic attacks and panic attacks can continue without cannabis use.
The relationship between cannabis use and agoraphobia, depersonalization, psychosis, and delirium has also been established. Panic attacks develop mostly in high doses and inexperienced users. Cannabis is the most frequently used illegal substance. It is thought that 200-300 million people regularly use cannabis in the world. The most common form of use of cannabis is cigarette smoking. When used like a cigarette, the effect of cannabis starts within a few seconds to a few minutes, reaches a peak at half an hour and ends in about 3 hours.
There is no precise information about the mechanisms by which cannabis causes panic attacks. It is reported that tetrahydrocannabinol (THC), the active metabolite of cannabis, may possibly be responsible for seizures and panic attacks. It has been reported that THC affects neurotransmitters such as dopamine, noradrenaline, and serotonin and benzodiazepine receptors. Since THC is known as the strongest active metabolite in cannabis, both positively and negatively, and with the evidence under the light of recent researches, it can be said that it is responsible for the seizures after cannabis use.
Can Cannabis Be Used to Prevent Epileptic Seizures?
According to a BBC report, some families in the United States give their children suffering from severe epileptic seizures cannabis oil, the raw material of marijuana. With the legalization of the production and sale of cannabis known as marijuana in the US state of Colorado, approximately 100 families who wanted to use the oil obtained from marijuana as a medicine. The medical benefit of Charlotte’s Love Network (Charlotte’s Web) has not yet been scientifically proven, referring to the name of one of the first children to be given the oil and the famous American children’s novel, but according to families, significant improvements have been observed in the condition of children with epilepsy. The hemispheric drug, a hemp-based pharmaceutical company based in the UK, is trying to develop a medicine produced using cannabis and has received prior approval from the US Federal Drug Administration.
- A Short History of Cannabis Plant
It is one of the oldest plants in human history. In history, cannabis had many uses such as yarn, weaving, fabric, paper, rope, biofuel, and soap. The cannabis plant was banned all over the world step by step after the obstacles to its cultivation with the ’Marijuana Tax Law” in the USA in the 1930s.
I don’t know how real it is that the giant American corporations of the time were put under the status of narcotic substances that undermined their earnings, thus preventing the use of cannabis in the plastics, paper, fuel, textile, pharmaceutical industries. In fact, there are 3 different plant species belonging to this genus. These are Cannabis indica, Cannabis Sativa, and Cannabis Ruderalis. The useful species is Cannabis Indica, which is known as Marijuana and is used as a recreational species. Cannabis species with many benefits have been discontinued because of prejudice.
In a recently published study, it is reported that: ” Our survey shows that parents are using cannabidiol-enriched cannabis as a treatment for their children with treatment-resistant epilepsy. Because of the increasing number of states that allow access to medical cannabis, its use will likely be a growing concern for the epilepsy community. ” (Porter et al., 2013).
The endocannabinoid system was first discovered in 1980. It consists of chemicals that keep the balance of the immune system such as mood, sleep, appetite, hormone levels, and pain. It works in the tissue it forms, does not participate in systemic blood circulation. Its half-life is very short. The main chemical of this system is called endocannabinoid. The cannabinoids produced by the body (anandamide, 2-AG) are different from herbal cannabinoids, which I will explain in a moment. Many human and animal studies have demonstrated that endocannabinoids play a role in memory, mental status, brain reward system and fat degradation, glucose metabolism, and energy balance. The receptors of the cannabinoids on the cell are 2 types. CB1 receptors are found in the central nervous system, liver, kidney, and lung in a small number, whereas CB2 receptors are part of the immune system.
- Synthetic cannabinoid mixture: Bonzai
Bonzai contains a synthetic cannabinoid mixture such as THC-like naphtholindole, JWH-018. It is 150 times more dangerous than cannabis and may be lethal. In some countries, cannabis use has been liberalized to combat Bonzai and reduce deaths.
Vegetable cannabinoids: CBD and THC
Two main cannabinoids, CBD and THC, are obtained from cannabis.
- THC (tetra-hydro-cannabinol)
THC binds to endocannabinoid receptors in the body and acts like a drug. It’s addictive. THC disrupts memory, shortens reaction time, increases heart rate, reduces concentration, dry the mouth, and causes red eyes.
- CBD (Cannabidiol)
What is of interest to us is herbal cannabinoid CBD. CBD reduces the effect of THC, activates different receptors such as vanilloid, adenosine, TRPV-1, and serotonin, has no drug effect, and is not addictive. CBD (by affecting neurotransmitter release via adenosine receptors) is involved in memory, learning, conscious movement, motivation and reward mechanisms.
CBD (via the 5-HT1A receptor) relieves depression-anxiety and has the effect of reducing sleep, pain and chemotherapy side effects. CBD (via the TRPV-1 receptor) plays a role in sensing pain at body temperature. Finally, CBD (by inhibiting the CPR55 signal) acts to inhibit bone density and blood pressure regulation and cancer cell proliferation.
Adverse effects: Insomnia at high doses, dry mouth, low blood pressure, tremor in Parkinson’s disease.
Israeli Ministry of Health is licensed CBD and THC in different rates for use in preventing cancer pain, chemotherapy side effects, phantom pain, pain associated with multiple sclerosis, diabetic neuropathy, spinal cord damage, post-traumatic stress disorder, severe Tourette syndrome, persistent epilepsy in adults and children, persistent Chron’s disease, and severe fibromyalgia. It is not advised to use for drug addicts and patients with heart failure.
In a 2016 study published in the Seizure magazine, a mixture of CBD and THC was tested and successful in 74 patients, most of whom had pediatric refractory epilepsy (using 7 anti-epileptics). Patients did not benefit from multiple epilepsy drugs and ketogenic diet therapy. Patient groups included in the study:
- Early-onset epileptic encephalopathy on a known genetic background (such as Dravet syndrome)
- Early-onset epileptic encephalopathy of unknown genetic background
- Congenital brain anomalies
The mixture was prepared such that the CBD dose was 1-20 mg/kg/day and the THC dose was 0.5 mg/kg/day. 89% of success was achieved in decreasing seizure frequency. There were positive effects on perception and language development in some of the patients, sleep problems and restlessness disappeared. Although there are problems in the fiction of the study, it is remarkable that it provides such great success.
In another review published in the Pediatrics magazine in 2017, all studies conducted so far have been reviewed and it is expressed that there is a need for new studies for accepting the benefits of cannabis use for Tourette syndrome, neuropathic pain, post-traumatic stress disorder, especially in Dravet syndrome and chemotherapy-induced nausea and vomiting.
CBD oil appears to be a third option in pediatric neurology physician control in children with epilepsy who use a large number of antiepileptic drugs that do not benefit from the ketogenic diet. Epidiolex is the first CBD drug to receive approval from the FDA in phase 3 trials. It seems that many drugs can be developed over the endocannabinoid system over time. Future potential uses of cannabinoids, if not now, are:
- Neurological diseases: Parkinson’s disease, Huntington’s disease, amyotrophic lateral sclerosis, multiple sclerosis, alcohol-induced neurodegeneration, traumatic brain injury, stroke
- Autoimmune diseases: Uveitis, systemic sclerosis, inflammatory bowel diseases
- Infection: HIV brain involvement
- Psychiatric disorders: Anxiety, personality disorder, attention deficit, hyperactivity, substance dependence, anorexia
- Cardiovascular: Reduce the formation of vascular clot plate
- Digestion: Intestinal motility disorders, chronic liver disease, alcoholic liver disease, intestinal diseases
- Diabetic nephropathy