A Brief Discussion of Cannabis Botany and the Endocannabinoid System

The cannabis plant is native to almost all climate zones, from Siberia to southern Africa, and is now thought to exist in three varieties: Cannabis sativa, Cannabis indica, and Cannabis ruderalis. Each variety has distinct characteristics. Cannabis sativa can grow to be very tall and tree-like, while Cannabis indica is usually short and bushy. Ruderalis is generally spindly and short, and has largely been ignored in both practical use and as the object of scientific study, though with the increased interest in both medical and industrial uses of cannabis, this, too, is changing.

Humans have used cannabis for thousands of years for a variety of purposes. Hemp fibers are thought to have been fashioned into rope, twine and cloth at least as long as 10,000 years ago and perhaps much longer, and were probably the source of the first paper made in China some 2,000 years ago. Human interaction with cannabis is probably much older, however. Some scientists have even speculated that cannabis and humans as well as other animals have co-evolved, because all vertebrates, which includes mammals, birds, fish and reptiles, have receptors for and produce substances known as endocannabinoids, substances that are nearly identical to compounds found in the cannabis plant, hence their name. Discovered only in the late 1980’s, the endocannabinoid system is one of a number of systems that help maintain balance, or homeostasis, in most body functions and systems. Because the endocannabinoid system is so vitally important, it has been the subject of thousands of research studies conducted around the world in recent years.

The endocannabinoid system’s role in human physiology is broad and multi-faceted. The central nervous system, the immune system, cardiovascular system, reproductive system, gastrointestinal and urinary tracts all contain cannabinoid receptors and are regulated by cannabinoids--with one important exception: the brainstem where, among other vital functions, respiration is controlled. This is why cannabis, unlike opiates, does not suppress breathing, even at high doses. Endocannabinoid production declines as people age, a process that may play an important role in the development of age-related and degenerative diseases such as atherosclerosis and cardiovascular disease, arthritis, osteoporosis and possibly a number of cancers as well as Alzheimer’s Disease and Parkinson’s Disease, as noted in our first installment.

And so it would seem to be a natural conclusion that replacing declining endocannabinoid levels with outside sources of cannabinoids would be desirable. As it happens, the only source of cannabinoids outside the human body is the cannabis plant. In our next segment we will explore how cannabis has been used as a medicine and why, after decades of neglect and even vilification, it is again assuming an important role in treating and possibly preventing a great many medical conditions.

Source:
http://amarimed.com/DOCBLOG/tabid/90/EntryId/5/A-Brief-Discussion-of-Cannabis-Botany-and-the-Endocannabinoid-System.aspx

Alan Shackelford, M.D. is principal physician of Intermedical Consulting, LLC and Amarimed of Colorado, LLC, and can be reached at DrAlanShackelford@gmail.com.

What About The Research?

According to a paper published in the Journal of Opioid Management in 2009, more than 15,000 peer-reviewed scientific and medical studies of the medical use of cannabis have been published world-wide and have shown conclusively that cannabis is an effective treatment for a variety of different medical conditions such as glaucoma, muscle spasms in multiple sclerosis, neuropathic and other kinds of pain, nausea, weight loss in wasting syndrome, and a number of psychological conditions including PTSD, Tourette’s Syndrome and seizure disorders. And as mentioned previously, compounds found in cannabis may prevent Alzheimer’s Disease, Parkinson’s Disease, and HIV-related dementia and may limit neurological damage from strokes and trauma. In this week’s installment, we will look the medical and scientific evidence supporting the use of cannabis to treat pain.

Cannabis has been used medicinally for a very long time. Its earliest documented use as an analgesic was in China some 2,800 years BCE, where it was used to treat gout and rheumatism. There is evidence that was used in Egypt some 800 years later, and by 1000 BCE its use was widespread in India. The Greeks are known to have used cannabis to treat pain around 500 BCE as did many tribes in Africa. Its modern use in Europe began with the publication in 1839 of investigations of its effects on the pain of rheumatism by W.B. O'Shaughnessy, a surgeon with the British East India Company and professor at the University of Calcutta.

More recent studies have demonstrated the efficacy of cannabis in alleviating acute pain resulting from chemical exposure, mechanical injury such as surgery and burns. Other studies have shown that cannabinoids are very effective in treating chronic neuropathic pain such as trigeminal neuralgia and pain from inflammation such as occurs in rheumatoid and osteoarthritis. Cannabis has also been found to be an effective treatment for migraine headaches and to enhance the effects of non-steroidal anti-inflammatory medications. Another study suggests that the endocannabinoid system may also be involved in the action of general anesthetics.

In addition to its remarkable effectiveness in relieving a variety of different kinds of pain, two other factors make cannabis a particularly good treatment for pain: its incredible safety and low toxicity. There has never been a verified report of a death due to cannabis in the more than 4,000 years of its use as a medicine. The same cannot be said of opiate analgesics, with deaths from opiates rising nearly 97% to more than 10,000 a year in American metropolitan areas between 1997 and 2002. Nor can it be said of prescription and over-the-counter non-steroidal anti-inflammatory medications such as indomethacin, aspirin and naproxen, medications frequently used to treat the more than 46 million Americans diagnosed with some form of arthritis. According to the June, 1999 New England Journal of Medicine, in the late 1990’s a conservatively estimated 16,500 patients with rheumatoid and osteoarthritis were thought to have died each year from the effects of these medications, a number that has continued to rise each year since then.

According to Article 18 of the Colorado Constitution, marijuana may be used by “…persons suffering from debilitating medical conditions…” , defined as cancer, glaucoma or HIV positive status or AIDS or their treatment, or a “…chronic or debilitating disease or medical condition, or treatment for such conditions, which produces, for a specific patient, one or more of the following, and for which, in the professional opinion of the patient's physician, such condition or conditions reasonably may be alleviated by the medical use of marijuana: cachexia; severe pain; severe nausea; seizures, including those that are characteristic of epilepsy; or persistent muscle spasms, including those that are characteristic of multiple sclerosis…” We will examine these conditions in detail in this and in coming installments.

Cancer, the first condition mentioned in Article 18, is characterized by the uncontrolled division of cells, and by their ability to spread into other areas of the body. The most common cancers in the United States are breast cancer, lung cancer, colon cancer and prostate cancer. Malignant tumors cause a variety of different symptoms, including pain, loss of appetite and weight loss and fatigue and many others. Many studies have shown that cannabis is particularly effective in alleviating the severe pain that accompanies cancer, especially in its later stages. One of them, a double-blind, placebo-controlled British study first published in 2005, showed conclusively that an extract of cannabis was much more effective than placebo in controlling pain that no longer responded to high-dose narcotic pain medications. These results have been verified in other studies, including a multi-center international study published in 2009.

Cachexia, or extreme weight loss, is often seen in cancer, but it also occurs in HIV infection and AIDS, congestive heart failure, severe COPD and anorexia from a number of different causes. A comprehensive review of 80 human studies published in 2002 found that the research evidence overwhelmingly supports the use of cannabis to treat loss of appetite and wasting in patients with cancer, while a similar literature review published in 2008 verified those earlier conclusions. A number of other studies also showed significant benefit in treating the wasting that is seen in HIV/AIDS.

Glaucoma is a condition usually characterized by an increase in pressure within the eye, and is thought to be the second leading cause of blindness in the world. A number of studies conducted in the 1970’s and ‘80’s showed that smoked or ingested marijuana lowered pressure in the eye, and in 2003 the American Academy of Ophthalmology issued a position paper detailing those effects. The position paper went on to say that marijuana was not superior to the prescription medications then available for treating glaucoma in either effectiveness or in safety. However, it did not address the problem that most if not all of the available prescription medications lose efficacy over time in many patients and that they could benefit from the use of marijuana to treat their glaucoma even after prescription medications had failed.

In coming weeks we will continue to examine the research supporting the conditions for which medical marijuana can be recommended in Colorado, and will highlight startling new laboratory research suggesting that cannabinoids may even kill cancer cells.

Source:
http://amarimed.com/DOCBLOG/tabid/90/EntryId/6/What-About-The-Research.aspx

Alan Shackelford, M.D. is principal physician of Intermedical Consulting, LLC and Amarimed of Colorado, LLC, and can be reached at DrAlanShackelford@gmail.com.

Medical Marijuana Studies in the Treatment of MS and Severe Muscle Spasms

People with MS and other diseases that cause severe muscle spasms, spasticity and tremors have used cannabis for a very long time, and have consistently reported that it relieves their symptoms. In what is perhaps the earliest medical report, Dr. William O’Shaughnessy, a British physician working in India, reported in 1842 that cannabis extracts effectively controlled the spasticity he observed in cases of tetanus, and in 1890, Dr. J.R. Reynolds reported in The Lancet that alcohol extracts of cannabis were effective in controlling painful muscle spasms. Little more was published until an informal 1974 survey of 10 patients with spinal cord injuries and muscle spasms found that more than half of them experienced decreased muscle spasticity using marijuana. This was followed in 1980 by a case report on two patients with nocturnal muscle spasms, one of whom had MS, that were relieved within 5 minutes of smoking marijuana. Abstaining from marijuana led to recurrent spasms that were again rapidly relieved by marijuana.
People with MS and other diseases that cause severe muscle spasms, spasticity and tremors have used cannabis for a very long time, and have consistently reported that it relieves their symptoms.  In what is perhaps the earliest medical report, Dr. William O’Shaughnessy, a British physician working in India, reported in 1842 that cannabis extracts effectively controlled the spasticity he observed in cases of tetanus, and in 1890, Dr. J.R. Reynolds reported in The Lancet that alcohol extracts of cannabis were effective in controlling painful muscle spasms.  Little more was published until an informal 1974 survey of 10 patients with spinal cord injuries and muscle spasms found that more than half of them experienced decreased muscle spasticity using marijuana. This was followed in 1980 by a case report on two patients with nocturnal muscle spasms, one of whom had MS, that were relieved within 5 minutes of smoking marijuana.  Abstaining from marijuana led to recurrent spasms that were again rapidly relieved by marijuana.
 
Over the next several years, a number of other case reports and small clinical trials confirmed these initial observations, but it was not until the 1990’s that trials with larger numbers of patients were conducted.  An anonymous survey of 53 MS patients in Britain and 59 MS patients in the US conducted by Dr. Paul Consroe and colleagues at the Department of Pharmacology and Toxicology at the University of Arizona revealed that more than 70% people with MS reported improvement in muscle spasms, spasticity and tremors with marijuana.  Patients also reported that it was helpful in improving bowel and bladder problems, difficulty walking, and loss of appetites and weight loss.
 
A similar survey conducted in 2002 by Dr. M. S. Chong at King's College Hospital in London in the UK showed that nearly half of all MS patients were regularly using marijuana to control their muscle spasms, and that 76% of British patients would use it if it were legally available.
 
More recently, GW Pharmaceuticals, a UK-based company, reported that clinical trials of its cannabis extract called Sativex involving 572 and 241 patients respectively showed significant reductions in muscle spasms when compared with placebo. Sativex, which
is administered as an oral spray, was approved by Health Canada in 2005 for use in treating neuropathic pain associated with MS, and has been used on a limited prescription basis in the UK and Spain for treating muscle spasms and pain associated with MS, with applications now under review for full prescription use in those countries and throughout the European Union.
 
Of greater importance is a finding reported in the journal Brain in 2003 that a synthetic cannabinoid provided “significant neuroprotection” in an animal model of multiple sclerosis. Dr. Gareth Pryce and a team of investigators at the Institute of Neurology at University College in London reported that "The results of this study are important because they suggest that in addition to symptom management, ... cannabis may also slow the neurodegenerative processes that ultimately lead to chronic disability in multiple sclerosis and probably other disease."
To test the findings of the 2003 animal study in humans, a 12-month study was conducted at the Peninsula Medical School in Plymouth, England. The results, published in the Journal of Neurology, Neurosurgery and Psychiatry in 2005, indicated that cannabis extracts may indeed slow the progression of MS, prompting a large-scale, 3-year study involving nearly 500 MS patients that is now underway at the same medical school. Results are not expected until the study ends in 2012, but if they verify the earlier findings, it would be a major advance in the treatment of MS.

Cannabis has also been shown to be effective in relieving muscle spasms and spasticity associated with a number of other illnesses such as irritable bowel syndrome, premenstrual dysphoric disorder (PMDD) and PMS, cerebral palsy, Parkinson’s Disease, amyotrophic lateral sclerosis (Lou Gehrig’s disease), spinal cord injury and other nerve injuries, and may also relieve the bronchial spasms that cause asthma, though little formal research has been done on cannabis in any of these conditions.

Source: http://www.amarimed.com/DOCBLOG/tabid/90/EntryId/11/Medical-Marijuana-Studies-in-the-Treatment-of-MS-and-Severe-Muscle-Spasms.aspx

Alan Shackelford, M.D. is principal physician of Intermedical Consulting, LLC and Amarimed of Colorado, LLC, and can be reached at DrAlanShackelford@gmail.com.

How is it that cannabis can be considered to have no medical benefit on the one hand, but can prevent Alzheimer’s Disease on the other?

The answer is as complex and convoluted as any mystery novel, with twists, turns and surprises and a cast of heroes, villains and innocent bystanders caught up in the action.

Angela O. was diagnosed with breast cancer in 2007 and has undergone a lumpectomy and radiation therapy. She has also been treated with a variety of different medications, including Taxol, a plant-derived medication that is used to prevent the spread of breast cancer cells. Mary B. was also diagnosed with breast cancer in 2007 and underwent a radical mastectomy followed by chemotherapy that caused such severe nausea that she was unable to eat until she was provided a different plant-derived medication that stopped her nausea completely within minutes of using it.

There is little difference in the effectiveness of either of their medications, but a world of difference in their status. Taxol can be prescribed by any doctor, while Mary’s medication—an extract of the cannabis plant--is considered by the Federal Government to have no medical benefit. Indeed, the Drug Enforcement Agency, or DEA, has classified it as a Schedule I drug since 1970, along with LSD, and heroin. Yet, in October, 2003, a patent was issued to the Department of Health and Human Services by the US Patent Office for the use of compounds found in cannabis as neuroprotectants to prevent Alzheimer’s Disease, Parkinson’s Disease and HIV-related dementia, and to limit neurological damage from trauma and the interruption of blood flow to the brain that occurs in strokes.

And, in yet another twist, after decades of support for the Schedule I classification of cannabis, in 2008 the American College of Physicians, the second-largest physician’s organization in the United States with 129,000 members, acknowledged the medical benefits of Cannabis and called on the DEA to remove cannabis from its current Schedule I status so scientists and doctors can more easily conduct research and use cannabis clinically. In late 2009, the largest physician group in the US, the American Medical Association (AMA), took a very similar position, also reversing a long-held opinion.

Source:
http://www.amarimed.com/DOCBLOG/tabid/90/EntryId/4/How-is-it-that-cannabis-can-be-considered-to-have-no-medical-benefit-on-the-one-hand-but-can-prevent-Alzheimer-s-Disease-on-the-other.aspx

Alan Shackelford, M.D. is principal physician of Intermedical Consulting, LLC and Amarimed of Colorado, LLC, and can be reached at DrAlanShackelford@gmail.com.

Medical Marijuana and Seizures, including those that are characteristic of epilepsy.

Another medical condition for which doctors can recommend marijuana in Colorado under Article 18 of the Colorado Constitution is “seizures, including those that are characteristic of epilepsy”. In this week’s installment we will examine what seizures are, followed by a discussion of why cannabis is sometimes used to treat them.

Seizures are defined as uncontrolled electrical activity in the brain or other parts of the nervous system and occur in people of all ages and races. Some people experience only one seizure and never have another, such as might occur with a high fever or as a side effect of a medication, while others may have many recurrent seizures. Only about 33% of people who have one seizure ever have another, while some 75% of people of people who have a second seizure will have subsequent seizures. This is called “epilepsy”, and some 3 million Americans have the condition. About 300,000 new cases are diagnosed each year, nearly half of which are in children under the age of 18. Conditions called “pseudoseizures” or “nonepileptic seizures” are seizure-like activity without any abnormal electrical activity in the brain and are not considered to be epilepsy.

Seizures are grouped into two large categories: generalized and partial seizures. Generalized seizures involve the entire brain or body, while partial seizures usually involve only certain parts of the brain or body. Generalized seizures include absence seizures, atypical absence seizures, myoclonic seizures, atonic and tonic seizures, clonic seizures, and tonic-clonic seizures. Partial seizures include simple and complex partial seizures and secondary generalized seizures.

Absence seizures, atypical absence seizures, simple and complex partial seizures and secondary generalized seizures usually do not involve involuntary muscle movements and may go unnoticed or be misinterpreted as daydreaming, while myoclonic, tonic and tonic-clonic seizures, which were once called “grand mal seizures”, are obvious and involve muscle stiffness or jerking, sometimes with loss of consciousness and falling.

Seizures may be caused by tumors, blood vessel malformations, or by strokes or lack of oxygen and may also occur after an injury to the head. They may also be the result of poisoning, such as with lead or other heavy metals, or infections, or as a side effect of a medication. In more than two-thirds of patients with seizures, however, no specific cause is ever identified.

When a seizure occurs, patients usually undergo a number of different medical examinations and tests. The electroencephalogram, or EEG, is a mainstay of seizure diagnostics. In an EEG, electrical activity in the brain is measured, and can often identify the location within the brain in which seizures begin. CT scans or MRIs are also often done to locate anatomic problems that may cause seizures.

If it is possible to identify an underlying cause for seizures, the specific disorder can often be treated, though in the more than two-thirds of patients in whom no cause is found, anti-seizure treatment is still indicated. This may include prescription medications or medical marijuana, or in some cases both.

It is important to note that the use of cannabis in seizure disorders has not been extensively studied. Although a large body of research evidence is unequivocally supportive of using cannabis in many medical conditions, the evidence supporting its use in seizure disorders is not quite so clear-cut, with some studies suggesting little benefit while others indicate that it is extremely beneficial. Please join us again next week as we continue to discuss epilepsy and the role cannabis can play in treating it, as well as the sometimes contradictory research.

Source:
http://amarimed.com/DOCBLOG/tabid/90/EntryId/8/Medical-Marijuana-and-Seizures-including-those-that-are-characteristic-of-epilepsy.aspx
 
Alan Shackelford, M.D. is principal physician of Intermedical Consulting, LLC and Amarimed of Colorado, LLC, and can be reached at DrAlanShackelford@gmail.com.

A Closer Look at Multiple Sclerosis

Because persistent muscle spasms characteristic of multiple sclerosis (MS) is specifically referred to in Article 18 of the Colorado constitution as a condition for which medical marijuana can be recommended, this week’s installment will discuss multiple sclerosis in detail.

It is difficult to determine how many people have MS. Estimates range from 300,000 to 500,000 in the US to 2.5 million worldwide. Some 8,000 new cases are diagnosed each year in this country. A 1982 estimate of the number of people with MS revealed that 2 Colorado counties, Weld and Larimer, have the highest number in the US, at 84 cases of MS per 100,000 people, followed by Olmsted County, Minnesota with 61 cases per 100,000 people. Caucasian women have the highest prevalence of MS. The prevalence (the number of cases per unit of population, usually 100,000) of MS rises with increasing distance from the equator, with the lowest prevalence in equatorial Africa, Asia and South America and the highest prevalence, 250 cases per 100,000 people, in the Orkney Islands in Scotland. The reasons for this are unknown, as are the exact causes of the disease.

The most widely accepted theory is that MS is an autoimmune disease in which T-helper cells, a type of white blood cell, attack the brain and the myelin sheath that surrounds nerves and acts something like insulation. These attacks are accompanied by a large outpouring of substances called “cytokines” that promote inflammation. Some medical scientists think the immune response is prompted by a viral infection, since antibodies to a number of different viruses have been found in patients with MS, though no consistent pattern has been seen. Environmental factors may also play a role, though this is also unclear.

The end result of this cascade of immune activity is damage to the myelin sheath and the white matter in the brain, interfering with the transmission of nerve impulses and causing symptoms ranging from vision problems due to optic neuritis (inflammation of the optic nerve), clumsiness, weakness, problems with balance, fatigue, neuropathic pain, tremors and muscle spasms. The disease usually takes one of four courses, the most common being relapsing-remitting MS in which symptoms wax and wane in an unpredictable way, with worse symptoms during active phases and relative recovery between attacks. In relapsing/progressive MS, there is usually little recovery between the worsening of symptoms seen in attacks, while in primary progressive MS, the symptoms worsen progressively. In relapsing/progressive MS, the least common form, the symptoms worsen continuously with remissions punctuated by frequent exacerbations.

No treatment has been found for MS itself. A variety of different immune suppressant therapies are used, including steroids, interferon beta-1b and beta-1a, Glatrimar (Copaxone), and a new class of medications called monoclonal antibodies such as natalizumab. Though these medications may slow the progression of the disease, none of them cures MS.

The damage to the white matter in the brain and the myelin sheath that interfers with nerve impulses causes the muscle spasms, stiffness and spasticity (continuous muscle tightness with superimposed cramping) that are among the more debilitating symptoms of MS. Spasms are unpredictable and sudden and can be very painful, interfering with most activities and sleep, while spasticity and stiffness make movement difficult or impossible.

Because these symptoms can be so devastating, treating them is a priority. A number of different medications are routinely prescribed, including diazepam, clonazepam, baclofen, tizanidine, clonodine and even Botulinum toxin. But these medicines display widely varying benefits, and patients have sought alternatives, among them cannabis. Because patients’ reports of rapid and long-lasting relief of muscle spasms with cannabis were so compelling, a number of studies have been done in recent years. As is so frequently the case in cannabis research, the number of well-designed trials is small, with only a relatively few patients involved. Nonetheless, the results have consistently demonstrated such significant benefit in treating the muscle spasms and spasticity associated with MS that one cannabis extract has been approved for clinical use in Britain.
 

Alan Shackelford, M.D. is principal physician of Intermedical Consulting, LLC and Amarimed of Colorado, LLC, and can be reached at DrAlanShackelford@gmail.com.