Almost all analgesic (pain-relieving) medication has limited efficacy for some types of pain. Medical marihuana is particularly useful because it has a broad spectrum of efficacy and a unique set of side effects.
Alzheimer’s is a degenerative disease that causes a progressive decline in brain function, and it specifically affects memory.
Amyotrophic lateral sclerosis (also known as Lou Gehrig’s disease) is a fatal neurodegenerative disease.
There are two common types of arthritis, rheumatoid arthritis and osteoarthritis, but both affect the joints, causing pain, swelling, and limiting movement.
- Rheumatoid arthritis is caused by the malfunctioning of the sufferer’s immune system. Instead of fighting off intruders such as bacteria or viruses, the body attacks the synovial membranes, which facilitate the movement of joints, eventually destroying cartilage and eroding bones. Rheumatoid arthritis is most common among the aged, whose immune systems are no longer as robust or efficient.
- Osteoarthritis, or arthritis of the bones, is also found primarily among the elderly, whose cartilage has been worn away through use. Arthritis may also manifest as chronic inflammation of the joints as the result of injuries.
Recent research is accumulating evidence that cannabis therapies are effective for arthritis and the other rheumatic and degenerative hip, joint and connective tissue disorders. Since these are frequently extremely painful conditions, the ability of cannabis to combat chronic pain makes it useful for that aspect, both on its own and as an adjunct therapy that enhances the efficacy of opiate painkillers. The use of cannabis as a treatment for musculoskeletal pain in western medicine dates to the 1700s.
Human studies have shown cannabis to be an effective treatment for rheumatoid arthritis.. Cannabis has a demonstrated ability to improve mobility and reduce morning stiffness and inflammation. Research has also shown that patients are able to reduce their usage of potentially harmful Non-Steroidal Anti- Inflammatory drugs (NSAIDs) when using cannabis as an adjunct therapy.
Modern research on cannabidiol (CBD), one of the non-psychoactive components of cannabis, has found that it suppresses the immune response in mice and rats that is responsible for a disease resembling arthritis, protecting them from severe damage to their joints and markedly improving their condition.
Medical researchers at Hebrew University in Jerusalem found in the metabolism of Cannabidiol an acid with potent anti-inflammatory action comparable to the drug Indomethacin, but without the considerable gastrointestinal side effects associated with that drug.
When the body metabolizes tetra-hydracannibinol (THC), one of the primary components of cannabis, it produces a number of related chemicals. At least one of these metabolites has anti-inflammatory and pain relieving effects. By modifying this metabolite, researchers at the University of Massachusetts Medical Center have produced a synthetic carboxylic acid known as CT-3 (also called DMH-11C, chemical name dimethylheptyl-THC-11 acid), which is more powerful than the natural metabolite and can be given in smaller doses. Animal tests found CT-3 effective against both chronic and acute inflammation; it also prevented destruction of joint tissue from chronic inflammation. The long safety record of marihuana – no one has ever died of an overdose – and the fact that a metabolite with the desired anti-inflammatory effect is produced in the body when marihuana is used, strongly suggest that safe and effective anti-inflammatory drugs in this class are possible.
CT3 has demonstrated analgesic effects in animals. In some cases the dose-dependent effect of THC was equivalent to morphine, but with a much greater duration of action. In contrast to the NSAIDs commonly prescribed arthritis sufferers, CT3 did not cause ulcers at therapeutically relevant doses. Moreover, it does not depress respiration, exhibit dependence, induce body weight loss or cause mutations. Studies on its mechanism of action are currently underway, with cytokine synthesis one of the pathways being studied.
Cannabis may also help combat rheumatoid arthritis by way of its established immune-modulation properties. Rheumatoid arthritis is characterized by deregulation of the immune system in response to an initial infection or trauma. Over-activity of the immune system’s B-cells causes antibodies to attack and destroy the synovial tissues located in the joint. The immune modulator properties of a group of fats found in cannabis known as sterols and sterolins have been used as natural alternatives to conventional rheumatoid arthritis treatments, which employ highly toxic drugs to either suppress the entire immune response of the body or to palliate pain and the inflammatory process without correcting the underlying immune dysfunction.
Cytokines play a role in either fuelling or suppressing the inflammation that causes damage in rheumatoid arthritis and some other diseases. The release of selected cytokines is impaired by cannabis, but the findings differ by cell type, experimental conditions, and especially the concentration of the cannabinoids examined. A sterol/sterolin combination has been experimentally demonstrated to reduce the secretion of the pro-inflammatory cytokines controlled by the TH2 helper cells and to increase the number of TH1 cells that regulate the secretion of antibodies from the B cells. This selective activation and inhibition of the immune system results is an effective control of the dysfunctional auto-immune response.
One of the unavoidable side effects of chemotherapy drugs used to treat cancer is the killing of healthy cells. Hence, following the chemotherapy treatments, the patient may experience various adverse effects like nausea, vomiting, loss of appetite and loss of control over the body. Medical marihuana is an effective natural antiemetic, which helps in overcoming nausea, thus allowing the patient to enjoy meals.
Traditional Cancer Treatments
Lung cancer, prostate cancer, breast cancer – in fact, most types of cancer all start the same basic way. Something causes cancer cells to divide and grow without pause, spreading badly damaged DNA. Those cells invade other tissues and, in most cases, form tumours.
Cancer studies have taken leaps and bounds as far as finding treatments to slow, and sometimes stop, the spread of cancer. However, two of the most important treatments, chemotherapy and radiation therapy, also cause damage and, often, severe side effects.
For instance, some of the most powerful, toxic chemicals are used in chemotherapeutic agents. Both treatments kill cancer cells, but healthy cells as well. Chemotherapeutic agents such as Adriamycin (doxorubicin) and Platinol (cisplatin) can, and have, caused immune suppression and multiple organ damage, but they also cause severe nausea and vomiting.
The vomiting can last over a period of days, to the point that some patients have actually torn their esophagus. Due to the vomiting and lack of appetite, severe dehydration and weigh loss is normal. In fact, many cancer patients begin having a reaction before chemotherapy begins, in “anticipation” of the side effects. Unfortunately, although chemotherapy and/or radiation therapy may be an integral part of their survival, many cancer patients decide not to take the therapies because the side effects are so severe.
Because of this, many are given a mix of anti-nausea drugs. Often, the anti-nausea drugs work. However, the drugs only give partial symptom control, while for others they give no control at all. In addition, those who take traditional medications may also suffer fever, bone pain, fatigue, anxiety, sleep problems and changes in heart activity, among other issues. This leaves cancer patients to suffer from the effects of the cancer itself, the side effects of the treatments, and the side effects of medications used to alleviate the initial side effects of the treatments.
Medical Marihuana for Cancer Patients
It has proven in many studies, performed by prestigious scientific and medical organizations and individuals, that medical marihuana can (and does) relieve pain and nausea. In fact, some of these studies go as far back as the 1970s and older.
For instance, in 1975, the New England Journal of Medicine published the results of a “double-blind” study on the effects of oral (ingested rather than smoked) tetrahydrocannabinol on nausea and vomiting. According to the study, “No patient vomited while experiencing a subjective “high”. Oral tetrahydrocannabinol has antiemetic properties and is significantly better than a placebo in reducing vomiting caused by chemotherapeutic agents.”
A 1999 report by the Institutes of Medicine concluded, “In patients already experiencing severe nausea or vomiting, pills are generally ineffective, because of the difficulty in swallowing or keeping a pill down, and slow onset of the drug effect. Thus an inhalation (but, preferably not smoking) cannabinoid drug delivery system would be advantageous for treating chemotherapy-induced nausea.” A possible option for patients who do not want to smoke marihuana is inhalation using a vaporizer.
Although freedom from nausea and vomiting are two of the most noticed benefits of medical marihuana use, many have reported a reduction in the severity of wasting away. As well, they’ve notice a lessening in depression and other “side effects” brought on by the disease, including an increase in appetite. All of these things together have helped many cancer patients live a better, happier, more comfortable life.
Over twenty major studies in the past nine years have shown that cannabinoids (the chemicals in cannabis) actually fight cancer cells. In fact, it’s been shown that cannabinoids arrest cancer growths of many different forms of cancer, including brain, melanoma and breast cancer. There’s even growing evidence that cannabinoids cause direct anti-tumour activity.
Since the possibility was first realized, many more studies have been conducted, focused on the possibility of cannabinoids have anticarcinogenic effects. A 2007 study by the Institute of Toxicology and Pharmacology in Rostock, Germany focused on human cervical cancer (HeLa) cells. The cells were treated with specific cannabioids and THC. Even at low concentrations, MA and THC “led to a decrease in invasion of 61.5% and 68.1% respectively.”
The benefits of medical marihuana for cancer patients are clear when it comes to increased appetite, reduction of pain, wasting, vomiting and nausea, as well as depression. Although its anticarcinogenic effects aren’t quite as clear, ongoing research further points to the possibility that medical marihuana may actually be what many claim it is – a truly miraculous drug.
Nausea and Vomiting
Some anticancer drugs cause nausea and vomiting because they affect parts of the brain that control vomiting and/or irritate the stomach lining. The severity of these symptoms depends on several factors, including the chemotherapeutic agent(s) used, the dose, the schedule, and the patient’s reaction to the drug(s). The management of nausea and vomiting caused by chemotherapy is an important part of care for cancer patients whenever it occurs. Although patients usually receive antiemetic drugs that help control nausea and vomiting, there is no single best approach to reducing these symptoms in all patients. Doctors must tailor antiemetic therapy to meet each individual’s needs, taking into account the type of anticancer drugs being administered; the patient’s general condition, age, and related factors; and, of course, the extent to which the antiemetic is helpful. There has been much interest in the use of cannabis to treat a number of medical problems, including chemotherapy-induced nausea and vomiting in cancer patients. Two forms of cannabis have been used: compounds related to the active chemical constituent of cannabis taken by mouth and inhalation of cannabis. Dronabinol (Marinol®), a synthetic form of the active cannabis constituent delta-9-tetrahydrocannabinol (THC), is available by prescription for use as an antiemetic. In 1985, the U.S. Food and Drug Administration approved its use for the treatment of nausea and vomiting associated with cancer chemotherapy in patients who had not responded to the standard antiemetic drugs.
National Cancer Institute (NCI) scientists feel that other antiemetic drugs or combinations of antiemetic drugs have been shown to be more effective than synthetic THC as “first-line therapy” for nausea and vomiting caused by anticancer drugs. Examples include drugs called serotonin antagonists, including ondansetron (Zofran®) and granisetron (Kytril®), used alone or combined with dexamethasone (a steroid hormone); metoclopramide (Reglan®) combined with diphenhydramine and dexamethasone; high doses of methylprednisolone (a steroid hormone) combined with droperidol (Inapsine®); and prochlorperazine (Compazine®). Continued research with other agents and combinations of these agents is under way to determine their usefulness in controlling chemotherapy-induced nausea and vomiting. However, NCI scientists believe that synthetic THC may be appropriate for some cancer patients who have chemotherapy-induced nausea and vomiting that cannot be controlled by other antiemetic agents. The expected side effects of this compound must be weighed against the possible benefits. Dronabinol often causes a “high” (loss of control or sensation of unreality), which is associated with its effectiveness; however, this sensation may be unpleasant for some individuals.
Marihuana cigarettes have been used to treat chemotherapy-induced nausea and vomiting, and research has shown that THC is more quickly absorbed from marihuana smoke than from an oral preparation. However, any antiemetic effects of smoking marihuana may not be consistent because of varying potency, depending on the source of the marihuana contained in the cigarette.
To address issues surrounding the medical uses of marihuana, the National Institutes of Health convened a meeting in February 1997 to review the scientific data concerning its potential therapeutic uses and explore the need for additional research. The group of experts concluded that more and better studies are needed to fully evaluate the potential use of marihuana as supportive care for cancer patients.
Anorexia and Cachexia
Anorexia, the loss of appetite or desire to eat, is a common symptom in cancer patients. It may occur early in the disease or later, if the cancer grows and spreads. Cachexia is a wasting condition in which the patient has weakness and a marked and progressive loss of body weight, fat, and muscle. Anorexia and cachexia frequently occur together, but cachexia may occur in patients who are eating an adequate diet but have mal-absorption of nutrients. Maintenance of body weight and adequate nutritional status can help patients feel and look better, and maintain or improve their overall health. It may also help them better tolerate cancer therapy.
There are a variety of options for supportive nutritional care of cancer patients, including changes in diet and consumption of foods, enteral or parenteral feeding (delivery of nutrients by tube), and the use of drugs. An NCI-supported study to evaluate the effects of THC and megestrol acetate (a synthetic female hormone) used alone and in combination for treatment-related and cancer-related anorexia and cachexia completed patient accrual earlier this year. Researchers will compare the appetite, weight, and rate of weight change among patients treated with THC to patients treated with megestrol acetate or with both therapies. Researchers will also evaluate the effects of the drugs alone or in combination on nausea and vomiting, assess for toxic effects of the drugs, and evaluate differences in quality of life among those patients who were treated with THC.
The Institute of Medicine (IOM), part of the National Academy of Sciences, has published a report assessing the scientific knowledge of health effects and possible medical uses of marihuana. The IOM project was funded by the White House Office of National Drug Control Policy. The IOM released its report on March 17, 1999.
Copies of the report, Marihuana and Medicine: Assessing the Science Base, are available from National Academy Press, Lockbox 285, 2101 Constitution Avenue, NW., Washington, DC 20055; (202) 334–3313 or 1–888–624–8373. The full text of the IOM report is also available at http://www.nap.edu/catalog.php?record_id=6376 on the Internet.
The dystonias are movement disorders in which sustained muscle contractions cause twisting and repetitive movements or abnormal postures.
The movements, which are involuntary and sometimes painful, may affect a single muscle or a group of muscles such as those in the arms, legs, or neck; or the entire body.
Early symptoms of dystonia may include deterioration in handwriting after writing several lines, foot cramps, and/or a tendency of one foot to pull up or drag; this may occur “out of the blue” or may occur after running or walking some distance. The neck may turn or pull involuntarily, especially when the patient is tired or stressed. Sometimes both eyes will blink rapidly and uncontrollably, rendering a person functionally blind. Other possible symptoms are tremor and voice or speech difficulties. The initial symptoms can be very mild and may be noticeable only after prolonged exertion, stress, or fatigue. Over a period of time, the symptoms may become more noticeable and widespread and be unrelenting.
There are several types of Dystonia including Anismus, Torsion dystonia, Cervical dystonia, Blepharospasm, Oromandibular dystonia, Cranial dystonia, Focal hand dystonia, Laryngeal dystonia and Dopa-responsive dystonia (DRD) among others.
No one treatment has been found universally effective to treat all the different types of dystonia. Instead, physicians use a variety of therapies aimed at reducing or eliminating muscle spasms and pain.
Treatment has been limited to minimizing the symptoms of the disorder as there is yet no successful treatment for its cause. Reducing the types of movements that trigger or worsen dystonic symptoms provides some relief, as does reducing stress, getting plenty of rest, moderate exercise, and relaxation techniques. Various treatments focus on sedating brain functions or blocking nerve communications with the muscles via drugs, neuro-suppression or denervation. All current treatments have negative side effects and risks.
There are numerous types of medications that have proven helpful however they do come with a long list of side effects. Some of these medications can be sedating, especially at higher doses, and this can limit their usefulness.
No controlled study of marihuana in dystonic patients has been published, and the only study of cannabinoids was a preliminary open trial of cannabidiol (CBD) that suggested modest dose-related improvements in the five dystonic patients studied.(30) In mutant dystonic hamsters, however, the cannabinoid receptor agonist, WIN 55,212-2, can produce antidystonic effects.(153)
30. Consroe P, Sandyk R, Snider SR. 1986. Open label evaluation of cannabidiol in dystonic movement disorders. International Journal of Neuroscience 30:277-282.
153. Richter A, Loscher W. 1994. (+)-WIN55, 212-2 A novel cannabinoid receptor agonist, exerts antidystonic effects in mutant dystonic hamsters. European Journal of Pharmacology 264:371-377.
Epilepsy is a persistent (chronic) condition of the brain. It involves unpredictable abnormal electrical discharges or misfirings of brain cells (neurons).
This misfiring in the brain can cause episodes of bodily convulsions, loss of coordination, loss of consciousness or altered sensory states. These episodes are commonly called seizures. People with epilepsy have persistent and recurring seizures. One may be born with epilepsy, or may acquire it as a result of disease or injury.
Epileptic seizures are often classified as partial seizures or generalized seizures. Partial seizures are more common and start in an isolated part of the brain. Partial seizures can be described as either simple or complex. When a simple partial seizure occurs, a person retains consciousness. The person with epilepsy may experience uncontrollable twitching or stiffening in a limb. There may be a tingling sensation, a change in consciousness or an odd smell without a source. The subjective sensations that may warn of an impending event are called an “aura”.
Complex partial seizures cause an impairment of consciousness. During this type of seizure, a person may act confused, aimless, fidgety, emotional or disturbed. They are likely to have no memory of the event after it is over. A simple partial seizure may progress to a complex partial seizure and then become a generalized seizure as the abnormal electrical discharge spreads to the entire brain.
Generalized seizures involve abnormal discharges or misfirings in all regions of the brain and result in impairment of consciousness. Behavior during generalized seizures may range from a blank stare with little or no movement (petit mal or “absence” seizures) to dramatic bodily convulsions (grand mal seizures). During these convulsions, the patient may have difficulty breathing and turn blue. They may also bite their tongue and may lose control of urine or stool. When they regain consciousness, they do not remember the event and are very sleepy.
Epilepsy is conventionally treated with a class of drugs called anticonvulsants. Doctors prescribe anticonvulsants or antiepileptic drugs according to the types of seizures patients experience and how well the patient can tolerate the drug. Many patients have a poor response to these drugs even when taken in combination.
In addition to problems with effectiveness, there can be serious side effects resulting from the use of anticonvulsants. While these side effects do not always occur, they can include nausea, headaches, loss of hair, swelling of gum tissue, impotence, depression, poor coordination (ataxia), liver failure, depressed blood counts and even psychosis.
Some people with grand mal seizures say they can prevent their seizures entirely by smoking marihuana. Others, who suffer complex partial seizures, report that marihuana also curbs their symptoms and prevents loss of consciousness. Marihuana is not considered useful for treating petit mal or absence seizures and may even worsen them.
Some patients find that marihuana works in conjunction with other drugs they are taking. Others find that marihuana works best for them when it is used without other drugs. Either way, these epileptic patients have made marihuana a necessary part of their medical treatment.
People using marihuana to control epilepsy should be aware that withdrawal from any medication that controls seizures may leave you more susceptible to the seizures. Marihuana is no exception. Patients with epilepsy are advised to exercise caution when using oral THC because there is not sufficient knowledge about the convulsive or anti-convulsive properties of the single compound.
Fibromyalgia is a common syndrome in which people experience long-term, body-wide pain and tender points in joints, muscles, tendons, and other soft tissues.
Fibromyalgia has also been linked to fatigue, sleep problems, headaches, depression, anxiety, and other symptoms.
Causes, incidence, and risk factors
The cause of this disorder is unknown. Although none have been well proven, possible causes or triggers of fibromyalgia include:
- Physical or emotional trauma.An abnormal pain response.
- Areas in the brain that are responsible for pain may react differently in fibromyalgia patients.
- Sleep disturbances, which are common in fibromyalgia patients.
- An infectious microbe, such as a virus. At this point, no such virus or microbe has been identified.
Men and women of all ages get fibromyalgia, but the disorder is most common among women aged 20 to 50.
The primary symptom of fibromyalgia is pain.
- The exact locations of the pain are called tender points. Tender points are found in the soft tissue on the back of the neck, shoulders, sternum, lower back, hips, shins, elbows, and knees.The pain then spreads out from these areas.
- The pain is described as deep-aching, radiating, gnawing, shooting or burning, and ranges from mild to severe.
- The joints are not affected, although the pain may feel like it is coming from the joints.
- People with fibromyalgia tend to wake up with body aches and stiffness. For some patients, pain improves during the day and increases again during the evening, though many patients have day-long, non-stop pain.
- Pain can increase with activity, cold or damp weather, anxiety, and stress.
Fatigue and problems with sleep are seen in almost all patients with fibromyalgia. Many complain that they can’t get to sleep or stay asleep, and they feel tired when they wake up.
Other symptoms may include:
- Irritable bowel syndrome with gas, and alternating diarrhoea and constipation
- Memory difficulties and problems thinking clearly
- Numbness and tingling in hands and feet
- Reduced exercise tolerance
- Sad or depressed mood
- Tension or migraine headaches
Our bodies naturally make pain relievers called endorphins, but they also make other substances that can trigger pain relief in the so-called endocannabinoid system. This system seems to play a key role in many processes in the body, including modulating how we feel pain. Marihuana contains cannabinoids very similar to those that occur in the body naturally.
Fibromyalgia patients typically experience body wide pain and often take multiple drugs to deal with all the symptoms of this disorder. Marihuana may treat multiple symptoms, and some patients have reported seeing results.
The two problems with herbal cannabis, Silverman and other critics say: It’s a complex natural substance that contains about 60 different compounds with potentially medicinal effects, some of which may interact with one another. The other problem is that the amount of these various compounds may vary by batch, as marihuana is not synthesized but grown.
While Silverman says he has great hopes that synthetic medicines based on individual compounds in cannabis may one day help fibromyalgia patients (after appropriate randomized controlled clinical trials have been done), he argues that the real thing today is just too inconsistent.
“We think that there’s probably a role for that class of compounds, the cannabinoids in general, and it’s just a question of working out how that’s going to be put into practice,” says Mark Ware, M.D., an assistant professor in family medicine and anaesthesia at McGill University, in Montreal, and the executive director of the Canadian Consortium for the Investigation of Cannabinoids.
Researchers investigating anecdotal evidence that cannabis relieves some of the symptoms of inflammatory bowel disease (IBD) have discovered a potential new target for cannabis-derived drugs for treatment of the disease.
This finding, published in the journal Gastroenterology today, could bring new hope for the UK’s 90,000 – 180,000 sufferers of diseases like Crohn’s and ulcerative colitis* with the possibility that cannabis-derived drugs may help to heal the gut lining, which is damaged during the course of disease. Both Crohn’s and ulcerative colitis – often referred to under the umbrella term of IBD – cause patients’ immune systems to go into overdrive, producing inflammation in different areas of the gastrointestinal tract.
This inflammation can cause pain, urgent diarrhoea, severe tiredness and loss of weight, and is most commonly diagnosed in young adults of both sexes between the ages of 15 and 25. Patients with IBD who are also users of cannabis often report that their symptoms are alleviated following cannabis use, suggesting that the gut is able to respond to some of the molecules found in cannabis. Investigating this phenomenon, Dr Karen Wright and Professor Steve Ward from the University of Bath worked with colleagues at the Royal United Hospital in Bath to look at the interaction of cannabis with specific molecules, known as receptors, found on the surface of cells in the gut.
Examining gut samples from healthy people and IBD patients, the researchers looked at two specific receptors, called CB1 and CB2, which are known to be activated by the presence of molecules found in cannabis. They discovered that whilst CB1 is present in healthy people, the presence of CB2 increases in IBD patients as their disease progresses. The researchers believe that the presence of CB2 receptor only during the disease-state may be linked to its known role in suppression of the immune system. In other words, it is part of the body’s natural mechanisms that attempt to restore the normal healthy state of the gut. If so, this makes it an ideal candidate for the development of new cannabis-derived drugs to help IBD patients. They also found that the CB1 receptor helps to promote wound healing in the lining of the gut.
“This gives us the first evidence that very selective cannabis-derived treatments may be useful as future therapeutic strategies in the treatment of Crohn’s and ulcerative colitis,” said Dr Karen Wright from the University’s Department of Pharmacy and Pharmacology.
“This is because some extracts from cannabis, known as cannabinoids, closely resemble molecules that occur naturally in our body, and by developing treatments that target this system, we can help the body recover from some of the effects of these diseases.”
Ordinarily, CB1 and CB2 have the task of recognising and binding to a family of substances called “endocannabinoids” that occur naturally in our bodies. Once these receptors have detected the presence of specific molecules in their surrounding environment, a chain of biochemical signals is activated which culminates in switching immune responses on or off – depending on what their function is.
“The normal job of the CB1 and CB2 receptors is to help moderate diverse responses throughout the body, but their presence in the gut means that they could be useful targets for the development of cannabis-derived drugs for controlling the progression of IBD,” said Dr Wright.
Figures are from the National Association for Colitis and Crohn’s Disease. There is no national database of people with Crohn’s or Colitis – the figures are taken from estimates published by the British Society for Gastroenterology in 2004.
Glioma is a type of cancer that starts in the brain or spine. It is called a glioma because it arises from glial cells. The most common site of gliomas is the brain.
Massi P, Vaccani A, Bianchessi S, Costa B, Macchi P, Parolaro D
Department of Pharmacology, Chemotherapy and Medical Toxicology, University of Milan, via Vanvitelli 32, 20129 Milan, Italy.
Recently, we have shown that the non-psychoactive cannabinoid compound cannabidiol (CBD) induces apoptosis of glioma cells in vitro and tumor regression in vivo. The present study investigated a possible involvement of caspase activation and reactive oxygen species (ROS) induction in the apoptotic effect of CBD. CBD produced a gradual, time-dependent activation of caspase-3, which preceded the appearance of apoptotic death. In addition, release of cytochrome c and caspase-9 and caspase-8 activation were detected. The exposure to CBD caused in glioma cells an early production of ROS, depletion of intracellular glutathione [?] and increase activity of glutathione [?] reductase and glutathione [?] peroxidase enzymes. Under the same experimental condition, CBD did not impair primary glia. Thus, we found a different sensitivity to the anti-proliferative effect of CBD in human glioma cells and non-transformed cells that appears closely related to a selective ability of CBD in inducing ROS production and caspase activation in tumor cells.