Denis Petro, M.D., is a practicing neurologist and clinical drug researcher in Arlington, Virginia.
As discussed in an earlier chapter, marijuana (Cannabis sativa) has been employed as a medication since ancient times. In Chinese and Hindu medicine marijuana found use as an analgesic, spasmolytic, and hypnotic. In the nineteenth century, cannabis extracts were used to treat muscle spasms associated with tetanus and rabies. Many other reports were published about the beneficial effects of marijuana in epilepsy, migraine headaches, and neuralgia.
One of the most difficult problems for a physician to manage is spasticity. When nerve pathways in the brain or spinal cord are damaged, spasticity of muscles controlled by that nerve pathway develops after the injury. Thus following spinal cord injury, spasticity is present in muscles below the site of injury. Patients with spasticity complain of impairment in control of the involved muscle with loss of fine movement, loss of muscle control with flexion of the associated limb, intermittent uncontrolled contractions, and pain. In addition, the severity of spasticity is usually dependent on the location and size of the damaged nerve pathway.
While many neurologic diseases can disrupt nerve pathways, the most common disorders causing spasticity include stroke, cerebral palsy, and multiple sclerosis. The prevalence of these disorders is well over 600 per 100,000 individuals in the United States. To this group should be added the population of patients with traumatic brain and spinal injuries resulting from war, motor vehicle accidents, athletics, and violence. Well over 1 million persons in the United States have signs and symptoms of spasticity.
The goal of medical treatment is to normalize muscle activity in the affected area while minimizing side effects. The medical definition of spasticity is quite specific and distinguishes it from muscle spasm. Injuries to peripheral nerves such as in sciatica can cause localized irritation to muscles or muscle spasm. This finding is quite different from spasticity with important implications for treatment. Unfortunately, spasticity based on a fixed brain or spinal injury remains a challenge to the healthcare provider.
Marijuana in Spasticity
While the medical literature consists of the collected observations of physicians throughout the ages, nothing can surpass the impact of personal observation of a clinical response in an individual patient. For this author, the observations of patients in a neurology clinic in the 1970s proved to be a powerful stimulant of personal interest in the therapeutic potential of marijuana.
A 27-year-old man was referred to the neurology clinic for evaluation and treatment of his severe spasticity (Petro 1980). The patient had experienced several acute episodes of neurological impairment including vision loss and weakness of both legs. The weakness prevented him from climbing stairs without assistance, and his condition was made worse when he became overheated. These symptoms are typical for patients with multiple sclerosis, and his diagnosis was confirmed by the appropriate central nervous system (cNS) studies. In addition to the weakness and fatigability of the legs, he experienced frequent episodes of severe leg spasm in the evening and while in bed at night. The leg complaints were not relieved with the use of analgesics such as aspirin and Tylenol. He could not tolerate Valium or other antispasticity drugs due to their side effects.
At the suggestion of a friend, the patient tried marijuana. He smoked a marijuana cigarette in the evening when his symptoms of leg fatigue or spasms were intense. He stated that within a matter of minutes his symptoms were relieved. At the time of his initial clinic visit, he was asked to refrain from using marijuana and was scheduled for a follow-up visit in six weeks.
At the time of the second visit the patient described an increase in symptoms including leg pain, increased muscle spasm, and increased uncontrolled muscle contractions in the evening. He had experienced several episodes of urinary incontinence at night that were connected to the muscle spasms.
Bladder function can be affected by the loss of central motor control in spasticity. The patient's neurologic examination was consistent with the more prominent signs of spasticity, including extremely brisk reflexes and abnormal muscle tone. When the examiner moved the spastic limb, the increased muscle tone could be felt as an increased resistance.
At the patient's request, he left the clinic and returned one hour later. The neurologic examination was remarkable in that the findings of severe spasticity seen earlier were now absent. Deep tendon reflexes were now normal, and no abnormal reflexes were present. The classic neurologic sign of a CNS lesion is the Babinski reflex. When the outer portion of the sole of the foot is stroked with a blunt object such as a key, a pattern of toe response defines the reflex. An abnormal response indicates damage to motor centers in the brain or spinal cord. Dramatic changes in this reflex in a period of one hour are extremely unusual. The patient admitted to smoking a marijuana cigarette in the time between examinations. The case was presented to the attending neurology staff and discussed in conference. The consensus opinion was that conventional spasticity treatments offered little improvement over the patient's therapeutic use of marijuana. The patient has continued his pattern of marijuana use to control his symptoms of spasticity without adverse effects.
Marijuana appeared to offer this patient several advantages oyer conventional treatment. In normal practice the patient is given instructions to take the medication three or four times a day without exception. Unfortunately, many patients have good days and bad days with little to predict their symptoms. Since smoked marijuana is absorbed by the body rapidly, the effect is seen immediately, and one can titrate consumption to improve symptoms of spasticity without producing dysphoria or other CNS effects. On those days when spasticity is relatively quiescent, patients need not expose themselves to excessive medication. Needless to say, the cost of conventional drug treatment is much greater than the cost of homegrown marijuana.
This observation of the dramatic effect of marijuana on a spastic patient prompted review of the published literature supporting the muscle relaxant and analgesic properties of cannabis. Personal communication with surgeons involved in the care of veterans supported the beneficial effects of marijuana in those patients with traumatic spinal injuries and resultant spasticity. In these conversations, the use of marijuana was said to be very common in Veterans Administration patients with spinal injuries. The pattern of use was similar to the case seen in the clinic, with intermittent use to control increases in symptoms, especially in the evenings.
In a review of the medical literature, a single publication was found that reported a survey of ten males with spinal cord injuries who admitted to using marijuana. Five patients reported reduced spasticity, three patients noted no effect, and two patients did not suffer significant spasticity (Dunn and Davis 1974). Based on the observation of a dramatic effect in a single spastic patient and the indications in the literature that support marijuana in neurologic disorders, a rigorous study of marijuana in spasticity was undertaken.
Since marijuana is administered by smoking and can be difficult to administer in some patients not familiar with the technique, the oral formulation delta-9-THC was used in a double-blind, placebo-controlled, single-dose study (Petro and Ellenberger 1981). Considered the most "psychoactive" cannabinoid, THC might not be the best drug in patients with some neurologic conditions. At the time of the research, no other cannabinoids were available for use in patients. In this study, extreme care was taken to control conditions to insure scientific credibility.
Since spasticity includes a variety of signs and symptoms associated with the motor system, a precise clinical examination of the motor system was used to quantitate motor function. Motor reflexes were graded and strength measured. Nine patients with spasticity associated with multiple sclerosis were entered into the study. A trained observer examined each patient on three separate days, before and at 90-minute intervals after the oral administration of a capsule containing either 10 mg, 5 mg, or no THC. The observer rated muscle tone, motor reflexes, and muscle resistance to movement on a standard rating scale. In addition, the electromyographic activity of the quadriceps muscle in the leg was compared after each dose.
The results showed a beneficial effect of THC on muscle tone, reflexes, strength and electromyographic activity. The beneficial effects were seen at 90 minutes after the dose was administered and persisted for up to six hours. Side effects were recorded after each dose and were minimal. One patient reported feeling "high" after 10 mg THC and another reported feeling "high" after the placebo. No other side effects were noted. This study demonstrated that single doses of THC have an antispasticity effect with a favorable safety profile. The improvement in muscle tone and function was consistent with the observation of the first clinic patient who smoked marijuana to control symptoms of spasticity. This study was also reassuring in that no significant side effects were noted. If the most psychoactive component of marijuana is safe, one might expect that other cannabinoids may be even more effective on the motor system while sparing other CNS systems. While a single clinical study is of interest, the usual practice is to evaluate the body of evidence in support of a hypothesis. Fortunately, the observations described above have been supported by a series of reports by researchers throughout the world that confirm the efficacy of marijuana in treating the signs and symptoms of spasticity.
In a 20-day crossover study, oral THC (35 mg/day) was given to five patients with paraplegia associated with trauma (Truong and Hanigan 1986).
The patients had significant spasticity as a result of spinal injuries, and a series of neurologic tests including reflexes, muscle activity, and electrical measurements was recorded. All patients responded with a reduction in one or more measures of spastic activity during treatment with THC. The investigators documented an effect on the motor system at a site in the CNS but not at the peripheral nerve or muscle. This report is consistent with the initial clinical study and other animal studies that place the action of marijuana in the CNS affecting multisynaptic pathways. Since the location of the lesion causing spasticity in patients varies from one patient to another, one cannot generalize concerning the precise site of action nor can one predict the individual's response to marijuana.
In a publication from Germany, the effects of marijuana on the motor system in a 30-year-old male with spasticity associated with multiple sclerosis were presented (Meinck et al. 1989). This patient was confined to a wheelchair due to spasticity. He claimed that marijuana improved his motor system such that he could climb stairs and walk on even ground. In addition, he stated that his urinary system improved along with normalization of sexual function. He was asked to abstain from all drugs and was hospitalized for observation. On the fifth day in the hospital a range of motor function studies were conducted. The tests were conducted before and after the patient smoked a marijuana cigarette. Muscle force increased, tendon reflexes normalized, and other motor reflexes improved in a fashion similar-to those responses seen in other studies. Also, recordings of hand tremor demonstrated a reduction in tremor after smoking the marijuana cigarette. The researchers concluded that this study confirmed the previous publications in demonstrating the beneficial effects of marijuana in spasticity. In addition to the antispasticity action, the researchers postulated an analgesic action as an additional benefit in patients with spasticity. This publication from Germany in essence repeated the observations presented in the initial case report from the United States.
In summary, a series of clinical studies have been conducted that confirm the observation that marijuana has beneficial effects in patients with spasticity. The observations were made in patients with spasticity associated with either traumatic spinal injury or multiple sclerosis. The effect has been seen with marijuana and with one of the constituent cannabinoids, delta-9-THC. No significant safety hazards were found in the published reports.
With the body of scientific evidence to support therapeutic effects and an obvious need on the part of spastic patients for more effective treatments of their condition, one might anticipate wide interest in the pharmaceutical industry for a research program to develop marijuana to treat spasticity. A potential sponsor need only complete "Phase 3" to submit a New Drug Application (NDA) to the FDA. In Phase 3, a drug in development is administered to a large group of patients such that dose-response activity and the risk-benefit ratio can be assessed in comparison to conventional approved treatments. Data from at least several hundred patients exposed to the drug for time periods of up to one year are usually presented to regulatory authorities prior to drug approval. This phase of drug development may take three years to complete and will cost up to $10 or $20 million. A corporate sponsor will make the appropriate projections of sales over the period of exclusive marketing of a drug and then proceed if the numbers are favorable. Since marijuana is a natural substance potentially found in one's backyard, no corporate sponsor is willing to expend the resources required for FDA approval only to be undersold by a local gardener.
With the publication of well-controlled studies that support the efficacy of marijuana in spasticity, one can ask: how widespread is the use of marijuana in the treatment of spasticity? Over the past decade personal communication with patients and physicians involved in the care of patients with spinal injuries has included hundreds of letters and telephone calls. Very few of these individuals have been willing to confront the daunting task of requesting marijuana from the government using the regulatory process. The practicing physician has neither the time nor the resources to face the regulatory bureaucracy.
An example from my own experience will illustrate the existing degree of regulatory arrogance. On one occasion the paperwork to provide marijuana to a patient with spinal injury in Long Island was prepared and submitted. Three nronths after the submission of all forms, I received a telephone call from a New York state regulatory bureaucrat concerning the case. All questions concerning the case were answered in the conversation. At the end of the call, the questioner stated that to evaluate the case adequately he would need to meet with me in his office in Albany. Since all questions concerning the case had been answered, I felt that no personal interview would be necessary or any remaining concerns could be addressed by correspondence. The bureaucrat stated that if I was not able to take the time to travel to Albany, he was not motivated to approve the request. The request for compassionate use of marijuana for this patient was denied. The patient continues to use marijuana provided by a friend without the supervision of governmental bureaucrats.
Since the number of patients with spasticity is quite large and amounts to well over 1 million people in the United States, it takes no leap of faith to assume that the number of patients using marijuana for spasticity is at least in the tens of thousands. In a survey of patients with spinal cord injuries seen at the University of Wisconsin, 24 of 43 responders reported marijuana use in the year prior to the survey (Malec et al. 1982). Of the 24 patients using marijuana, 21 indicated a reduction in spasticity due to marijuana use. Simply stated, 88 percent of those patients who use marijuana reported improvement in spasticity. If this simple survey is in any measure a reflection of the data in the United States, use of marijuana for spasticity may be even greater than the tens of thousands noted above. With this widespread use in mind, the need to characterize the therapeutic index for marijuana in spastic patients is obvious.
THERAPEUTIC INDEX OF MARIJUANA IN SPASTICITY
The therapeutic index is a quantitative comparison of the therapeutic and untoward effects of a drug. For example, aspirin is effective in the vast majority of patients in the management of pain with only rare cases of significant adverse effect or fatality. Yet even with aspirin one can expect occasional severe or even fatal reactions, such as anaphylaxis or bleeding disorder. In the treatment of spasticity, one might ask whether marijuana is a reasonable alternative to traditional medical management of spasticity. The two major treatments for spasticity are dantrolene and baclofen.
Dantrolene (trade name: Dantrium) acts directly on skeletal muscle to increase the weakness of the spastic muscle. Since the drug is distributed throughout the body, all skeletal muscles are weakened including those distant from the area of spasticity. The dosage of dantrolene is begun at 25 mg daily and gradually raised to a maximum of 400 mg/day. Unlike marijuana, this drug subjects the patient to weeks or months of treatment ter' evaluate the potential effectiveness of dantrolene. In addition, CNS side effects, such as dizziness and drowsiness, are very common. If dizziness and drowsiness were the only problems with dantrolene, it might be considered a potential therapeutic agent. Unfortunately for the patient, dantrolene can cause hepatotoxicity, which can be fatal. Symptomatic hepatitis occurs at higher doses, and this effect is of such severity as to warrant a "box warning" in the labeling of the drug. The liver impairment can occur at any time and is more common in females, in patients over 35 years of age, and in patients also taking other prescription drugs. Liver function studies must be monitored to watch for impending disaster. Even though the drug is administered for chronic use, the long-term safety of dantrolene has not been established. In animal studies, hepatic and breast tumors were increased at high doses. As one can see from this brief description, dantrolene is a drug with a low therapeutic index and of limited value to the clinician.
Baclofen (trade name: Lioresal) is considered the most useful drug in spasticity not related to stroke. Baclofen works at sites in the CNS to increase inhibition of the motor system. In use, the drug is started at a dose of 15 mg daily and increased slowly to a maximum of 80 mg/day after two weeks. The drug is associated with sedation and unsteadiness of movement although tolerance to these effects will occur over time. While generally considered safer than dantrolene, baclofen can cause side effects including hallucinations, anxiety, and tachycardia (rapid heart rate) after abrupt drug withdrawal. For this reason, baclofen should be decreased slowly over four weeks for withdrawal. Lower doses are recommended in patients with impaired renal function. Patients with a history of stroke do not respond well to baclofen and have a poor tolerance for the drug. Use of baclofen in pregnancy is not recommended because of animal studies showing an increase in fetal abnormalities. Additional questions of safety were raised in the finding of increased ovarian cysts in female patients treated with baclofen for up to one year.
Recently, a new method of administration of baclofen has been approved in the United States. In this technique, baclofen is delivered by direct infusion into spinal fluid using a programmable infusion pump. The infusion system is implanted beneath the skin and a catheter is used from the pump to the spinal canal. This technique is reserved for those patients with spasticity who are unresponsive to oral baclofen or experience intolerable CNS side effects at usual therapeutic doses. Spinal infusion is considered an alternative to direct neurosurgical procedures such as cutting the motor nerve to the spastic muscle. Placement of an infusion pump is not without risk. The infusion pump must be appropriately positioned beneath the skin and must be placed in a patient of sufficient bulk to accept the device. Complications include battery failure, infection, movement of the device, and catheter blockage or kinking. In addition, the possibility of a drug administration error cannot be ruled out. In the premarketing studies, 13 deaths occurred in the 438 patients'reported to have used the system. The relationship between the device and a fatal outcome could not be determined, but at least some patients may be at risk of death in association with this therapy.
Other drugs used in spasticity include the benzodiazepines, such as Valium, phenothiazines, and anticonvulsants. Valium acts in a manner similar to baclofen and inhibits synaptic transmission in the CNS. All of these agents are considered less effective than baclofen or dantrolene. Since no single agent is satisfactory, the clinician usually proceeds by trying the drugs in sequence, beginning with baclofen, dantrolene, the secondary drugs, and then going on to invasive methods such as baclofen infusion and to neurosurgical procedures such as cutting the involved motor nerves. The approach begins with the safest and most efficacious methods and proceeds to the more invasive and dangerous ones. With this review as background, one may ask whether marijuana should be considered as a treatment for spasticity.
Based on the brief review herein, one can safely say that marijuana is certainly no worse than several generally recognized approaches that have been implicated in patient fatalities. In recorded history, no evidence has been published relating the oral or inhaled exposure to marijuana to a fatal outcome. Fatal hepatotoxicity secondary to dantrolene is a documented finding.
Baclofen is considered much less dangerous than dantrolene, but the safety of baclofen is not unquestioned. The development of baclofen infusion is an admission of the failure of the oral formulation in many cases.
Many spastic patients have developed symptoms as a result of multiple sclerosis. Recently, interest in the treatment of multiple sclerosis has focused on interferon beta (Betaseron). Betaseron has shown some positive effects on exacerbation rates, severity of exacerbations, and CNS lesions. Unfortunately, the effect on neurologic disability has been less dramatic. Since spasticity is one of the many symptoms associated with multiple sclerosis, only time and clinical experience will provide clear answers to the questions concerning Betaseron. Since Betaseron may slow the progression of the underlying disease, extra years of productive life may be added with therapy. The treatment does not reverse areas of previous injury that might be found in patients with spasticity.
In addition to the clinical considerations regarding therapy, an important aspect of treatment of spasticity is the cost associated with medical care. The financial cost of ongoing physician care and drug therapy for spasticity can range to the thousands of dollars per year. In a time when rationing of health services is a consideration, an incentive exists to use only "conventional" treatments covered by health insurance. Certainly, a physician has little incentive to recommend marijuana if such a recommendation will lead to governmental censure even in the face of the evidence supporting marijuana in spasticity. In personal conversations with many physicians who have inquired about marijuana as treatment for spasticity over the years, the overwhelming majority has agreed with the position that marijuana has potential as a therapeutic agent. Unfortunately, the governmental obstacles to marijuana prescription remain daunting for practicing physicians. Without a corporate sponsor with deep pockets, the current situation will not change. After nearly 20 years of experience and at least several pendulum swings in regulatory approach, the prospect for a rational policy concerning medicinal marijuana remains still very much in doubt.
From the scientific evidence substantiating the efficacy of marijuana in treating spasticity, several conclusions can be drawn. Over the years, patients have self-medicated with marijuana to treat signs and symptoms of spasticity. Relief of spasms, improved muscle tone, and relief of discomfort have been commonly seen. Support for this observation has been obtained in well-controlled clinical trials. The risk-benefit ratio or therapeutic index for marijuana can only be characterized by large, long-term studies comparing marijuana with conventional treatments. At present, conventional treatments for spasticity are unsatisfactory. Based on scientific evidence, cannabis is an effective and safe alternative when compared to conventional treatments. Where cannabis and cannabis derivatives will ultimately be placed in the practice of medicine, a more enlightened society will decide. Separation of the therapeutic uses from the concerns regarding abuse should be a goal of all parties in this issue. Perhaps by the dawn of the millennium, answers to the clinical issues may be forthcoming.
Marijuana in Movement Disorders
With the reports of the beneficial effects of marijuana in spasticity, a series of studies were published on patients with other disorders of the motor system. In one report, a patient with multiple sclerosis noted decreased postural tremor of the head and neck after smoking marijuana. Postural tremor is the involuntary regular and repetitive shaking of a body part associated with sustained posture. The investigator then studied eight multiple sclerosis patients with disabling tremors and ataxia (Clifford 1983). Ataxia is an abnormality of movement characterized by errors in rate, range, direction, timing, duration, and force of motor activity. A series of neurologic tests of the motor system was carried out and compared before and after test doses of THC. Two of the eight patients were judged to have both subjective and objective improvement in motor function after THC. In a separate report, five patients with Parkinson's disease and severe tremor were studied. Marijuana was compared to Valium and conventional anti—Parkinson treatment. None of the patients improved on marijuana or Valium while conventional drugs such as levodopa, and apomorphine were effective.
The cannabis derivative, cannabidiol (cm), has been studied in a few patients with dystonia (Consroe et al. 1986; Snider and Consroe 1985). Dystonia is the slow, purposeless, involuntary movements affecting muscle groups of the face, neck, limbs, and trunk. Cannabidiol has fewer CNS dysphoric effects than delta-9-THC. In several reports, patients with dystonia of the head and trunk have responded to CBD. Like the other cannabinoids, CBD is an extremely interesting potential therapeutic agent. As with the other compounds, without a sponsor to support the costs of research, CBD will not be the subject of widespread study.
Marijuana in Chronic Pain
Since analgesia is ultimately expressed at the level of the central nervous system, neurologists often are consulted in managing patients with difficult pain problems. During residency training in a pain clinic, a 30-yearold female was seen to evaluate her pain management. She had received multiple injuries in a motor vehicle accident including fractures of the pelvis, right kneecap, the fifth lumbar vertebra, and multiple ribs. Her recovery was complicated by persistent muscle contraction pain of the neck and lower back. Her treatment included medication such as meperidine, pentazocine, and Valium.
When first seen in the clinic her neurologic examination was normal except for tenderness of the neck muscle area and a sensory loss to touch in the left shoulder region. She complained that her medication caused excessive sedation and interfered with her ability to work. In addition, she expressed concern regarding the addiction potential of her medication. Since the analgesic and muscle relaxant drugs she was using have been associated with serious untoward effects, several alternative approaches were tried. Acupuncture was attempted over a three-week course without effect. Transcutaneous electrical stimulation was likewise unsuccessful. Upon the recommendation of a physical therapist, the patient began using marijuana for her neck pain and tenderness. The physical therapist had experience in the hospital system of the Veterans Administration and suggested that marijuana was one of the options tried in post—Vietnam era veterans with neuromuscular problems. The patient tried marijuana in periods when her symptoms increased and used simple aspirin on occasion. Over a period of three months, she eliminated the use of all prescription drugs. The patient reported both analgesic and muscle-relaxant effects without the sedation associated with her opiate and benzodiazepine cocktail previously required.
On a separate occasion, a 34-year-old female was seen after experiencing a side effect associated with the treatment of migraine headaches. The patient experienced three to four classic migraine episodes per month with visual symptoms followed by prolonged headache, nausea, and photophobia. She could not tolerate beta-blockers or opiate analgesics. Her use of ergot antimigraine therapy had resulted in disturbing sensory changes in her arms and legs. As a "last resort" she tried smoking marijuana at the first sign (aura) of an impending headache. To her surprise, the severity of her headaches decreased dramatically. The frequency of her episodes dropped to one per month over the next year. Throughout the year she carried a marijuana cigarette for use only in an "emergency."
As in the case of spasticity, interesting observations on the use of marijuana in cases of pain have been reported over the years. Reports in the nineteenth century included use against the pain of rheumatism, neuralgia, menstrual cramps, and childbirth. The use of marijuana for these indications decreased with the development of drugs such as aspirin and the opiates. Interest in the cannabinoids as analgesic agents was renewed with the synthesis of more than 40 cannabinoids isolated from the cannabis plant in the last 30 years.
Drug development in the analgesic field has been explosive since World War II. Potent analgesics are essential in time of war, and access to opiates has influenced the conduct of wars over the ages. The localization of specialized brain receptors involved in the perception of pain has been successful and the effects of analgesics at these sites is well known. The cannabinoids have been studied in many models of pain with effects as great as those of standard" analgesics such as morphine and codeine.
The methods used to evaluate analgesics in clinical trials have been generally recognized and standard zed. New drugs are compared with standard drugs such as aspirin or codeine in models of pain such as postoperative dental renal colic and arthritic pain and in cancer cases. Since a wide variety of therapeutic agents are marketed, and the total analgesic market amount to billions of dollars, the regulatory requ rements for new analgesics include many studies on large numbers of patients. The regulatory barrier to a new cannabinoid analgesic agent would be extremely difficult to overcome since the drug would most likely be considered to have a potential for abuse and would be restricted by the DEA. Wth the wide variety of competing analgesic agents that do not face DEA restrictions a corporate sponsor would not be willing to venture into the regulatory waters with a new cannabinoid analgesic agent
Several interesting cynical studies using cannabinoids as analgesics have been published In healthy subjects THC was shown to produce analges'a to a heat source In cancer patients with severe pain oral THC (10 mg) was equal in effect to codeine (60 mg). Higher doses of THC induced CNS side effects Researchers are directing their efforts to manipulate the basic cannabinoid structure to retain analgesic action and imit sedation and other CNS side effects. ,
The evidence in support of cannabis as a treatment for pain exists both preclinical animal studies and in a small number of clinical trials Since cannabis contains many act've cannabinoids in varying amounts in differing plants, a coherent recommendation concerning use against pain symptoms is lacking Some patients may prefer marijuana to a cocktail of prescription drugs or, as in the case of the migraine patient, they may choose it to obtain a dramatic effect Others may benefit from effects associated with marijuana such as appetite stimulation n patients with cancer or AIDS Considering the alternative of addicting drugs such as the opiate analgesics, patients may opt for the relative safety of cannabis. Fatal overdose continues to be a significant problem with the opiates. The absence of any fatalities associated with cannabis remains an astonishing fact. The safety profile of cannabis is such as to allow the clinician to consider this treatment option in selected cases, such as cancer and severe chron c pain with manifestations such as depression, weight loss, or intolerance of opiates.
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