White Buffalo Productions
 

 Marijuana:  Dangerous Drug or Medicine?

         Since marijuana was removed from the pharmacopoeia in 1937, there has been a continuous debate as to whether it has a value as a medicine.  There is perhaps, no other medical debate in which opinion is so divided.  One group of doctors views marijuana as one of the most dangerous substances known to man, a stepping stone drug that is unsafe for human consumption under any circumstance.  Robert Dupont, former head of the National Institute of Drug Abuse during the Reagan Administration, was a strong advocate of this position.  He concluded in a 1986 report that becasue marijuana breaks down into 2,000 chemicals when smoked, it will be a long time before it is possible to understand it's mechanism of action, and therefore it is unsafe for consumption.[1] In a recent article in the New York Times, "Debate on Using Marijuana as Medicine Turns to Question of Whether It Works,"  the current medical opposition to the use of marijuana as medicine was summarized.  Dr. Bennett of Oregon Health Sciences University, an expert on high blood pressure and kidney disease  whose son died suddenly with cocaine in his blood stated: "Marijuana has never been shown safe and effective for anything- not one single study. . . It is very second line therapy, surpassed by modern drugs. . .I have compassion, believe me, but desperation is not the basis for social policy."  Dr. Erye, chief medical officer at the American Cancer society states  "The bottom line is that the evidence to support marijuana as being superior to any other agent is very minimal to none. . .the scientific data, are very fragmented and poor."[2]

          In total contrast to this scientific position is another group of doctors who view marijuana as a medicine of unparalleled value and potential. Dr. Raphael Mecholam, a former researcher at Tel Aviv University who in 1964 first synthesized delta-9-tetrahydracannabinol (THC), the psychoactive ingredient marijuana, is one such researcher.  In a 1982 Omni magazine article he stated that marijuana was capable of replacing 10-20 % of all pharmaceutical prescription,  and would most likely be included in 40-50% of all medicines when research was completed.[3]    Lester Grinspoon, Harvard Medical School,  began investigating  marijuana in the 1960's believing that young people who were turning to it for symptomatic relieve were endangering their lives.  By 1971 when he published his completed research in his book, Marijuana Reconsidered, his opinion had been radically transformed.  After a complete review of all scientific and medical evidence, he became convinced that he, like the rest of the public, had been brainwashed about the effects of marijuana on humans,  concluding that all medical evidence clearly demonstrated that marijuana is safer than alcohol or tobacco.  He recommended its legalization.[4]

          While debates over the therapeutic efficacy of pharmacological agents are not new to modern medicine,  a unique feature of the debate over the use of marijuana as a medicine is that it is the longest and most expensive debate in United States Medical history.  Since the mid-1960's when marijuana became popular among college students, and strongly associated with the Anti-war movement,  there have been over 6000 journal articles written concerning different aspects of the marijuana issue.   No one could challenge the evidence that more studies exist on the use and abuse of marijuana than any substance single illegal substance in the world, and enough studies exist to construct an argument for or against its use.  If science is an objective tool for analyzing data and determining the ultimate truth,  how are such divergent opinions possible? 

Paradigm and Scientific Revolution

          In 1964 Thomas Kuhn provided a compelling look at history of science in his book, The Structure of Scientific Revolution, which examined how science evolves.[5]  According to Kuhn's thesis, when anomalies or new data arise which can not be explained by existing theories a crisis slowly develops.  The reason a crisis develops is because unexplainable data undermines scientists' theories of knowledge that is the foundation of their training, and professional careers.  A crisis can only be abated when a new theory capable of explaining all existing data comes into existence.  Science itself is so stagnant and rigid in Kuhn's estimation that frequently only when society becomes so frustrated that it demands that science come out from its reclusive hiding place and address the issues at hand, that most crisis get solved. According to Einstein, science and religion shared a common goal;  the elimination of pain and suffering for humankind.  In this sense for a scientist to accept crisis is to admit a crisis in faith, never an easy thing for anyone to do, but for a scientist, it sometimes means acknowledging that his entire career has been spent pursuing a path that is not necessarily based on truth. 

          To symbolize the chief characteristic that was responsible for making science stagnant and resistant to change, Kuhn coined the phrase "paradigm."  Paradigm literally means to show by example.  It has become a mainstay of the scientific community, as scientists frequently refer to this or that paradigm when trying to describe different systems of science.  But to Kuhn paradigm was something much deeper than a system of science.  A paradigm defined the conditions and initiation process an individual must endure to become a member of the scientific community.  The nature of the initiation rights are used to create the world views and values that eventually define the problems and methods for the study of science; Kuhn  writes:

       ...to understand why science develops as it does, one need not marvel the details of biography and personality that lead each individual to a particular choice, ...What one must understand, however, is the manner in which a particular set of shared values interacts with the particular experiences shared by a community of specialists to ensure that most members of the group will ultimately find one set of arguments rather than another decisive."[6]

Kuhn's insights that paradigm is responsible for the inherit inability science to adapt to change has important implications for government policy towards research, and the role the history of science plays in solving deep paradigmatic crisis  by alerting the scientific community to historical developments.  The

          (Insert Figure 1)

Historical difficulties in establishing a policy concerning marijuana as medicine is represented in the diagram above.  What are the differences between sacraments, drugs and medicines?  E.O. Wilson proposed in his 1975 best seller, Sociobiology, that much of sociological research up to that point in history had relied on observation, and labeling of phenomena, or culture, without a clear understanding of biology.  The major obstacle interfering in the establishment of a scientific policy concerning marijuana can be traced to a culture represented in the JUST SAY NO policy toward drugs that based its entire policy on labeling of phenomena and ignoring scientific data.  This not only effected the questions that were are asked, but ultimately influenced how experiments were arranged, and results were interpreted.  The importance of this is that up to this point in history our policy toward the medical use of marijuana has been based on labeling of cultural phenomena without regards to science.  E.O. Wilson proposed that neurobiology would in the end become  a the ultimate basis of sociology and psychology.  Neurobiology was the key to understanding normal and abnormal human behavior.  If you watch the nightly news human behavior appears to be at the root of the current crisis in our communitys.    Kuhn demonstrates with a variety of historical examples that crisis has been the catalyst for many scientific revolutions of the past. 

        "a novel theory emerged only after a pronounced failure in the normal problem-solving activity. .... (the) breakdown and proliferation of theories that is its sign occurred no more than a decade or two before the new theory's enunciation.  The novel theory seems a direct response to crisis."[7]

          A recent discovery challenges the entire foundation of the "Anti-marijuana paradigm introduced by Dupont, and signals the time for a dramatic change in the course of policy.    The first step in correcting our policy failures is this area require recognition that our early science in this area that dominated research dollars and programs of public mis-education were based on "cultural" reactions to drug use and not science.  Judging from the difficulties the US has in regards to drug use and abuse, How a society chooses between drugs, medicine and sacraments can have dangerous consequences for society? 

          It was originally assumed that marijuana's pharmacological action was non-specific like alcohol and that its effects were due to disruption of cellular membranes.  The discovery of a dose dependent curve for  different cannabinoids was a sign that marijuana does not have a non-specific action.   The discovery of a cannabinoid receptor and endogenous ligand which appear to be specific for THC suggest that a novel theory that ends once and for all the debate over marijuana as medicine can finally be relegated to the museum of science.

The Cannabinoid Receptor and Endogenous Ligand

          In 1988 William Devane, a post doctoral student working in the lab of Allyn Howlett proved the existence of the cannabinoid receptor.  On August  9,  1990 the debate over whether marijuana is medicine officially ended, when it was reported in Nature that a cannabinoid receptor had been successfully cloned, and a corresponding messenger RNA found in the cell lines and regions of the brain where the receptor has been located.[8]  Receptors have now been located in the basal ganglia particularly the striatum,  the hippocampus, the cerebellum, the cerebral cortex, the testes, the marginal zone of the spleen, and there is growing evidence that there are also spinal chord receptors.[9]  In December 1992 Devane and Mechoulam reported the isolation and purification of an endogenous ligand which they named anandamide. (see figure 2 below) It

(Insert Figure 2)

means "internal bliss" in Sanskrit.  After reviewing the data,  Solomon Synder, famous for the discovery of the opiod receptors, called this a breakthrough of  enormous consequence.     There has never in the history of neurobiology been the discovery of a receptor without biological, behavioral and medical significance.  Bill Martin Virginia Commonwealth University states  "This has greater implications than just the study of marijuana.  We will be learning about an entirely new neurochemical system."[10]  The questions that remains are those that are asked after the discovery of any new neurotransmitter or 2cd messenger in the brain.  What are its neurobiological properties as a medicine?  Is it safe as a medicine?  What are its mechanism of action?  What are the doses responses?   What are the risks? And finally potentially  the most intriguing question of all "What role do anadamide-making neurons play in the central nervous system." 

          This report attempts to reexamine previous medical research into the medical uses of marijuana in light of the new discovery of a receptor and an endogenous ligand.   I believe that it is in the realm of neurobiology that the entire of debate over the use of marijuana as medicine is laid to rest when we recognize that marijuana's therapeutic effects although complicated can be explained by its unique pharmacological properties. 

Is it safe?

          During the Bush and Reagan administration substantial sums of money were spent trying to prove that marijuana impaired immune function.   A review of the literature shows that the majority of studies on the negative effects of marijuana on the immune system were done using concentrations of marijuana that are unscientific.[11]  Marijuana concentration in the blood upon casual use is usually between 10-9 and 10-10.  For instance, a recent study demonstrated that 4, 10 or 25 puffs on cigarette with either 1.75 or 3.55 % THC, brings blood levels from 57 to 268 ng/ml [12]  The majority of immunity studies have been done for concentration of 10-4.   In other word,  these research studies are on the effects of 1,000,000 joints/day.   A scientist can achieve any result he wants if he chooses inappropriate measurements.  1,000,000 anything per day will kill most human beings.  In a review of the literature, "Marijuana and Immunity," Hollister states that most studies have been seriously flawed by the very high concentrations of drug used to produce immunosuppression, and by the lack of comparisons with other membrane drugs.  The closer that experimental studies have been to actual clinical situations, the less compelling has been the evidence.[13]   In the first ever human study on the effects of THC on endrocine and immunological function, Dax et al at NIDA reported no effects on the immune system.  "Since no significant alterations were observed either in the acutely treated subjects or in those reporting heavy THC use, we suggest that at least some of the previously described immunosuppressive effects of THC may be nonspecific effects secondary to very high doses."[14]

          In 1975 the most extensive study on the health effects of marijuana was completed by V. Rubin and L. Comitas, called "Ganja in Jamaica."  The study was a matched control of 30 heavy chronic cannabis smokers who had averaged up to 420 mg of THC per day for an average of 17.5 years.  All participants were examined in the hospital for 6 days and given a complete battery of psychological, and medical tests.  There were no substantial differences in physical or mental health of either group.[15]   

          The modern standard for determining the safety of a medicine for human consumption are done by measuring the effective dose vs. lethal dose.  In 1972 these tests revealed that marijuana has the safest  therapeutic index of any substance ever discover.  There is not one recorded death from marijuana overdose in the history of medicine.  A comparison of the safety factors for secobarbital, alcohol and marijuana is below.[16]  

 Safety-

                   Effective                          Lethal                             Safety Factor                              Dose                     Dose                              (Lethal Dose/

                                                                                               Effective Dose)

Secobarbital  100-3-- mg                   1,000-5,000 mg                 3-50

Alcohol           0.05-0.1%                             0.4-0.5%                   4-10

Tetrahydro-   50 mcg/kg                           2,160,000 mcg/kg*           40,000*

cannabinol

*  Because no human fatalities have been documented, the figure given are for the human effective dose and the lethal dose for mice.

          Marijuana has been sited as potentially dangerous for people who suffer high blood pressure or extreme anxiety.  This author believes that this class of patient might be able to use marijuana effectively as we begin to understand its pharmacological effect more clearly.  It is important to keep in mind that all medicines are potential dangerous, marijuana is no different.  Further research is needed to understand who these patients are, but there is no scientific doubt that marijuana is as safe as any pharmaceutical drug on the market.  Annually almost twice as many deaths occur from pharmaceutical drugs as compared to deaths from all illicit substances.   In fact we might expect that if all pharmaceuticals underwent the severe test period that marijuana has we probably would not have a pharmacopoeia at all.

Marijuana in Medical History

          The use of marijuana in medicine goes back some 4000 years in history.   The legendary Chinese Emperor Shen Neng whose name means the "Divine Cultivator" and is considered the father of Chinese medicine was responsible for including marijuana in the first herbal in 2737 B.C.  The Chinese pharmacopoeia divides medicines into 3 classes.  The first class is for the treatment of specific symptoms, for example, headache, diarrhea.  This lowest class of medicines is for after disease is diagnosed.  The second class of medicines is for the prevention of illness.  Only recently has western medicine recognized the importance of prevention in medicine, a concept that was fundamental to the Chinese conception of illness from its beginnings.  The last class of medicine is for the pursuit of immortality which in Chinese medicine is associated with attaining the age of 100 years old.  To be in this class of medicines, a substance had to promote longevity, be nonpoisonous and safe to use over a long period of time.[17]  Marijuana is listed in this higher class of medicines.  

          The medical applications of marijuana were first studied by W.B. O'Shaughnessey a physician trained at Edinburgh who in 1839 working at the medical College of Calcutta found marijuana useful for rabies, rheumatism, epilepsy, and tetanus.  In 1842 he introduced cannabis to pharmacists in England.[18]  Among the early enthusiastic supporters of the medical uses of marijuana was Dr. Reynolds, Queen Victoria's physician,  who prescribed marijuana for her for PMS and menstrual cramps.  Writing in the Lancet in 1890 he states,  "When pure and administered carefully, (it) is one of the most valuable medicines that we possess."[19]   

          One of the most striking observation about marijuana's use as medicine is in just how many different disorders it has been used for over the years. T.H. Mikuriya after doing a complete review of the historical literature, Marijuana: Medical Papers, in 1969, listed the following potential therapeutic applications for marijuana:  analgesic-hypnotic, appetite stimulant,  anti epileptic- antispasmodic,  prevention and interruption of the neuralgia, including migraine and tic douloureux, antidepressant, psychotherapeutic aid, anti asthmatic, oxytoxic accelerates child birth, antitussive, topical anesthetic, an agent that facilitates withdrawal from opium and alcohol, childbirth analgesic, antibiotic.[20]  Modern research has demonstrated that marijuana may also be effective for glaucoma, depression, anorexia, multiple sclerosis, treatment of pain and inflammation, lowering of intraocular pressure, and nausea associated with chemotherapy.   

          The next logical question for neurobiology is, Does the discovery of a receptor, coupled with the recent studies of the neurobiological effects of marijuana help explain its mechanism of action for treatment of disease, or are we dealing with a placebo or antidotal reaction related to its subjective mood enhancing effects?  

 Receptor Location and Mechanisms of action-

          Marijuana contains some 400 separate compounds at least 60 of which have been recognized as having therapeutic value.[21]  Understanding its precise mechanism of action on individual neurons is still some what unclear.  This is partially due to the fact that besides its own receptors, it also appears to effect a range of neurotransmitters, most likely through 2cd messenger pathways.  Nevertheless, we known more about its mechanism of action than most currently available pharmaceuticals.  Because marijuana was banned from research in the United States in 1976,  most current studies focus on the two most powerful active ingredients of marijuana, THC, the main psychoactive ingredient of marijuana, and cannabidiol (CBD),  which has strong anti emetic, anti seizure, and anti-tremor properties.  The chemical structure appear in diagram 2 below.  It has now also been suggested that there may indeed be several sets of subtypes.

(Insert Figure 3)

          Neurobiology and Real Estate share a common component, location, location, location.  The cannabinoid receptor through animal studies is most highly concentrated in the striatum, the cerebellum, and the hippocampus. 

          The striatum consists of the putamen and the caudate nucleus.  They serve as input nucleus or relay stations for the entire basal ganglia.  They receive input from the motor cortex, supplementary motor cortex, somatosensory cortex.  Both the motor and somatosensory cortex have complete representation of the entire body, a point that will be important in later discussions of this paper.  It is generally agreed that the basal ganglia are important for planning and execution of motor movement.[22] Bidaut-Russell Michelle, and Howlett, Allyn C. have demonstrated that the cannbinoid receptor in the rat striatum works by regulating c AMP production.[23]   Howlett et al have also suggested that cannabinoid inhibits adenlylate cyclase through a G-protein[24], and that in striatum, dopaminergic, opiod, and cannabanoid receptors may be present in the same population of cells.[25] These studies suggest a very definite role for a modulatory effect of THC on muscles and movement.  Marijuana differs from opium in that it relaxes striated muscle, but not smooth muscle of the viscera.  Marijuana's medical use for the acceleration of childbirth, muscle spasticty, and possibly its anti-epileptic properties are likely connected striatum receptors. THC also effects both serotonin re-uptake, and the production of tyrosine hydroxalyse the rate limiting step in the synthesis of al catecholamines.  The figure below diagrams the role of cAMP, and adenlylase cyclase in the neuron.

(Insert Figure 4)

          The cerebellum has a high density of cannabinoid receptors.  The cerebellum contains only 10% of the brains weight, but 50% of all neurons.  It was one of the last structures to develop from the stand point of evolution.  The cerebellum is important in execution of movement, and posture by controlling the descending motor pathways.  It provides internal feedback for motor and pre-motor cortex, and external sensory feedback from the periphery.  There are 2 complete somatotopic representation in the cerebellum.  The cerebellum has been implicated in motor learning as cerebellar circuits are modified by learning.[26]  

          The hippocampus is the final area which seems to have a large number of  cannabinoid receptors.  The hippocampus is part of the limbic system involved in regulation emotion or affect, and by connection with the hypothalamus for modulation of the autonomic nervous system.  The hippocampus plays an important role in memory storage.  Damage to the hippocampus can lead to the inability to form new memories.  During Alzheimer's disease, the area where neurofibullary tangles and amyloid plaques

(Insert Figure 5)

 form causing memory dysfunction.  The figure above shows the pathology of hippocampus associated with Alzheimer's disease.  Projection through the hippocampus lead to frontal cortex and areas of association which are involved in long term memory and poteniation.  Landfield et al reported that high doses of THC decrease the volume of hipppocampus neurons and nuclei in rats, and at low doses there is a shortening of dendrite spines.[27]  Okada et el. report that marijuana has a bi-phasic effect on K+-evoked Ca2+ responses in rat brain synaptosomes, at concentration of 10-10, K+-evoked Ca2+ were enhanced, while at 10-9, K+-evoked Ca2+ channels were inhibited.  He cites this as verification of  Kujtan et al. and Nowicky and Teyler who found bi-phasic changes in hippocampal slices, concluding that THC through its effect on Ca2+.  Calcium

(Insert Figure 5a)

regulation is important for long term poteniation and facilitation in the nervous system.  (see figure 6) I would suggest that it appears that marijuana may be a unique pharmacological agent for modulation of long term memory, a concept that will be explored in depth using Post Traumatic Stress Syndrome, and  drug addiction as two examples of its potential as an aid to psychotherapy.

Arachidonic Acid-

          The endogenous ligand for THC appears to be a simple derivative of arachidonic acid. Arachidonic Acids (AA) are known to have effects on inflammation, injury, and control of smooth muscle in blood vessels and lung.[28] The study of arachidonic acid has been difficult becasue it appears to be made on demand.  It is a by-product of phospholipase A2, , and diglyceride lipase a by-product of phospholipase C.  AA is found in low concentrations 10-10 in the nervous system, and is part of a group of Eicosanoids (E) with 2cd messenger capacities.  (see figure 6) It has been postulated that E series prostoglandins a  by product of arachidonic acid modulte NE, and block

(Insert Figure 6)

convulsions, increase cAMP in cortical and hypothalamic slices in vitro.  There is little information for intact animals however.[29]  The figures below show several potential pathways for archidonic acid.

[Insert Figure 7]   

Another by product of AA, 12-HPETE,  has been shown by Bliss et al. to inhibit long term poteniation in rat hippocampal cells.[30]   Steger et al. studying the effects of THC and CDB on the Hypothalamic- Pituitary Axis demonstrated an suppression of plama-luteinizing hormone(LH) and Testosterone levels, and median eminence NE turnover , but no dose dependent curve could be established.  The decrease in LH appeared to be due to a reduction in NE stimulation of luteinizing hormone releasing factor (LHRH).  THC caused a significant decrease in the adrenal contents of both norepinephrine and epinephrine significantly increasing the E/NE ratio.   No effect on tyrosine hydrolase activity was found. [31]  Murphy et al. showed that "THC blocked the ability of E estradiol desensitize pituitary cells to inhibitory influence of dopamine.[32]  While most studies have focused on the ill effects of marijuana on the hypothalamic-pituitary axis, these same studies suggest a role for marijuana is modulation of the stress reaction, the fight or flight response first recognized by Walter B. Cannon.

          The diverse mechanisms of action of marijuana and its two most active ingredient CBC and THC clearly explain possible mechanisms of action for the diverse number of medical application of marijuana, a few specific examples are outlined below.  

Spatiscity- Multiple Sclerosis-

          Mecholam has demonstrated in a series of animal experiments that CBD can block seizure,  reduce symptoms of neurological diseases such as Huntington's disease.[33]  Cannabinoid receptors show evidence of strong  anti emetic, anti seizure, and anti-tremor properties.  Lester Grinspoon newest book, Marijuana: Forbidden Medicine, reports case histories of patients with multiple sclerosis, and paraplegia and quadriplegia who found marijuana beneficial in relieving symptoms.[34]  The receptors in the striatum  and cerebellum are both most likely responsible for this unique action.  It also suggests that marijuana might be beneficial in a host of other striatal diseases including Parkinson's,  Huntington's, Chorea, or any disease where spasticity is common like spinal chord injury, muscular dystrophy, cerebral palsy.    

          Maurer et al in a double blind study comparing THC- 5 mg, 50 mg codeine and placebo in patient with spasticity and spinal chord injury.  Both codeine and THC showed analgesic properties but only THC showed anti-spasticity properties.  The dose, 5 mg, was well below the psychoactive level.[35]

          Clifford reported the history of a patient with debilitating tremor of head and neck that made it difficult to eat and all therapy previous failed.  THC relieved tremor within 30 minutes and lasted for 6 hours.  A placebo had no effect.[36]  Melnick et al. working at University of Gottingen, report the results of electromyography study of leg reflexes, and electromagnetic recording of hand tremor in a 30 year old man with MS who used marijuana for motor and sexual problems. [37]

          The primary symptoms of MS are parestesias,  muscle spasm, genral fatique and weakness.  Current therapies for muscle spasticity usually involve GABA agonists, bacolefen or valium.  Baclofen is only moderately effective, and it has major side effects, the worst being that it causes drowsiness and fatigue both of which are already major problems in the management of MS, and all chronic diseases.  The body develops a tolerance for bacolfen very quickly, and patients usually must rely on increasing doses.  Approximately 75% of patient report fatigue and drowsiness as side effects of baclofen.  GABA agonist also inhibit sexual function, a side effect many patients are uncomfortable discussing with their doctors.  Scientifically an argument could be constructed that challenges the idea of using a GABA agonist which increases inhibition of motor function in the basal ganglia and cerebellum with people who already have difficulty with motor control and coordination.  Secondly, no longer term studies exist to test the long term effects baclofen might have on the course of multiple sclerosis, something that deserves study.

          The location of receptors for THC and CBD suggest a primary role for  controlling tremor, and spasticity.  GABA agonists were first prescribed for spasticity becasue of the high concentration of GABA receptors in the cerebellum.  There is increasing evidence that the newly discovered THC receptors are more specific for muscle spasticity and tremor.  When compared for cost effectiveness and side effects marijuana is superior to baclofen in every respect.  For patient who dislike the 'subjective or euphoric' effective of marijuana a relatively small dose orally, .5 gram in herbal weight, at bed time is extremely effective.  From a cost effective basis bacolefen is expensive, as much as $5/day, and it is metabolized so quickly it needs to be taken 4-6 times per day to be effective. 

          Conroe et al. in a study which used CBD,  700mg/day orally to Huntington patients, n=14,  found means plasma level 5.9-11.2 ng/ml over 6 weeks.  One week after the discontinuation of therapy plasma level dropped to  1.5 ng/ml, the half life of CBD estimated to be 2-5 days.  The low bio-availibility of cannabinoids suggests that they are neutralized by stomach acid, or are absorbed poorly.[38]  This low bio-availibility is one of the reasons that smoking the marijuana is most effective becasue it allows a patient to carefully titrate their dose with rapid absorption. While many have criticized marijuana as medicine because of the fact that it stays in the blood for so long, plasma 1/2 life 2-5 days,  this is precisely why it is so effective against spasticity or muscle dysfunction.  When using marijuana for chronic conditions such as muscle spasm, this is precisely one of its benefits.  It is easy to maintain a blood level necessary for spasticity control. 

Multiple Sclerosis- Marijuana as a modulator of the immune system

          MS is believed to be an immune-mediated disease in which the immune system turns against the nervous system and destroys the myelin sheath, and stops it from regenerating.  Grinspoon reports the case history of a man who has had MS for 20 years.  For the first 10 years of the disease he took the standard medications for MS,  baclofen, valium, ATCH.  One afternoon he became semi-catatonic and was rushed to the emergency room where it was discovered that his blood was totally depleted of potassium, upset at the side effects of the drugs and the fact that he was now bed ridden, he swore off the use of pharmaceutical medications.  He soon began to smoke marijuana for a way to kill boredom.  One night while friends were visiting and they had smoked a couple of joints, he spontaneously stood up without thinking about it, and walked.  While this may seen anecdotal,  he from time to time stopped using marijuana only for the symptoms to reappear. 

          Lyman et al report from Albert Einstein College that THC is effective in preventing and stopping the animal model of MS, Experimental Auto Immune Encephalomyelitis (EAE).   Rats and guinea pigs were administered EAE either before or after they were injected with THC.  In the Placebo group more than 95% died in 15 days.  While in the THC group there was a 95 % survival rate.  A neurological examination upon death revealed a significant reduction in inflammation. concluding THC has been shown to inhibit both clinical and histological EAE, and may be important in the treatment of immune related disorders.[39]

          Clinical tests in this area are imperative.  There is only one current therapy for MS, beta-interferon.   The results of beta interferon test with MS patients which was approved by FDA in April are not particularly promising.  From 372 patients in high, low and placebo groups,  the annual number of attacks or exacerbation was,   p=.84, 1.17, 1.27 respectively.  Only 36 patients were without symptoms in the high group, 23 in low dose and 17 on placebo.  Again, the cost of beta-interferon is extraordinarily high, almost $1,000/month.   While brain lesions were less in the high and low dose groups when compared to placebo there was no differences in disability or function.[40]   If we assume that 21 patients achieved a significant result out of 336, the cost effectiveness of beta-interferon comes into question.  At $12,000 per year the cost of improving 21 patients to normal health was $8,064,000. 

          This is a perfect example of how paradigm can effect science in a negative manner.  The pharmaceutical industry and the FDA now essentially run on money, not science.  Marijuana has been tested extensively for 30 years,  and yet the FDA and NIH have dragged their feet on a issue of substantial importance to patients health and pocketbooks.  Beta-interferon after less than 3 years of study, and no long term perspective is now in the pipeline for $500 million in sales by the end of this year.  The point being that money spent on clinical trail of marijuana will be well worth the expense because in the long term marijuana as medicine significantly reduces patient's annual costs for medication.  Marijuana as medicine will save consumers as much as $20 Billion per year.  

Cancer

          Mark Kleinman , a drug researcher at Harvard's Kennedy School of Government who interviewed cancer specialists from around the US, was shocked to find that 50% of all doctors recommended marijuana to their patients.[41]        Noyes et al. in experiments comparing  THC, codeine and placebo in cancer patients found that THC was equivalent to codeine, and recommend that further research should be done on THC  considering its relatively few side effects and low potential for abuse.  Sacks et al. did a case report on a patient with Hodgkin's disease, receiving intensive intineoplastic therapy and found a   reduction of nausea and vomiting, stimulation of appetite, and an improvement in mood.  Food intake during chemotherapy without THC was less than 1/2 that with THC.  Marinol, a new synthetic form of THC manufactured by Roxane Laboratories, Columbus , Ohio was used.[42]  Marinol recently approved as an orphan drug, costs approximately $1000/day as compared to pennies a day when using marijuana.  Cost effectiveness is a real issue.   

          In 1976 research studies were initiated by the DEA and Ford  administration to try and demonstrate that marijuana was harmful to cancer patient.  One such study at the Medical College of Virginia was done to demonstrate that THC made tumors grow out of control.  When THC was injected into tumors in 1975, they showed a substantial reduction in size.  The National Institute of Health intervened with the DEA and asked that all experimentation be stopped.[43]  With the discovery of THC receptors on the spleen, a careful examination of marijuana's use by cancer patients is called for.  All previous studies of chemotherapeutic action that did not control for the use of marijuana are called into question.  Only through clinical studies will we be able to determine is marijuana has effects on survival rates of cancer patients, and patients with other illnesses.  

Depression and Disorders of Mood

          Mechoulam believes that receptors for marijuana are directly related to mood and emotional states (1991)[44].  In the past year another drug reported to have a similar affect on mood,  Prozac or fluoxetine, has had sales of over $1.2 billion dollars.  It mechanism of action for depression is to inhibit the reuptake of serotonin.[45]   Johnson et al. found that THC  inhibited the reuptake of serotonin.[46] and also increased the biosynthesis of serotonin by increasing the availability of tyrosine hydroxylase.[47] [48]  THC has the classical tri-cyclic structure.  A comparison THC (figure 3) with fluoxetine HCL, and two biogenic amine uptake blockers are shown in Figure 8.  Central nervous system

(Insert Figure 8)

deficiencies of 5-hydroxytrptamine (serotonin) was first implicated in depression in 1962 by Praag and has been clearly implicated in some forms of depression.[49]  Low levels of serotonin have been associated with aggressive behavior particularly suicide, while high levels of serotonin have been associated with obsessive-compulsive disorder.  THC may have a modulatory effect of serotonin levels in addition to its specific effect on cannabinoid receptors.

          A derivative of marijuana synhexyl was one of the first substances ever tested for depression.  In 1947 Stocking demonstrated an impressive success rate in the treatment of depression he states:

       ...My findings confirm that the drug is a powerful euphoriant with a specific action on the higher centers...The general effects are... a pleasant feeling of happiness and exhilaration with a marked sense of relief from tension and anxiety, and the threshold for unpleasant affect is markedly raised, while the pleasant feeling-tone is correspondingly lowered.  There is increased enjoyment of normal pleasant impressions, and the zest for life and working capacity may be actually increased in the early stages of intoxication... A generalized feeling of warmth diffused throughout the body is characteristic.[50]

          Approximately 70% of patients who went through the study showed substantial improvement.  Many authors have criticized marijuana's euphoric or subjective effect on mood calling it a serious problem in using it in medicine.

Leslie L. Iversen, states in an Nature article, "Medical uses of marijuana?.

"The exploitation of the possible medical benefits of marijuana, however, has always been limited because of its powerful psychoactive properties, and there is currently no approved medicinal use in the United Kingdom."[51] Another researcher states, "Pfizer had a very intensive program for cannabinoids, but ...we couldn't separate the pharmacological effects."[52]  

          For years empirical scientists have been trying to duplicate marijuana's unique pharmacological properties by creating in the labortory a  drug without a psychoactive component.  This approach fails to comprehend the impertance of the mind/body dynamic in the healing process.  It is this author's belief that one of the main difficulties in understanding the diverse action of marijuana as medicine is that it has a unique pharmacological characteristics which can only be understood from a psychosomatic or mind/body paradigm.  Psychoneuroimmunology (PNI) is said to represent "the emergence of an important interdisciplinary area whose roots lie in neuroscience, immunology, ethology, psychology, neurology, anatomy, psychiatry, epidemiology, and endocrinology. . . it purports to go beyond conventional biomedical interactions of behavior and physiology, i.e. , how thought, feelings and action may linked to the immune system activity and therefore to health and disease."[53]  One of the benefits of marijuana in the treatment of chronic illness is that by elevating mood, it may also have PNI benefits.   

 AIDS- Why further studies are needed

          It is common knowledge in the AIDS community that marijuana is extraordinarily beneficial in helping patients cope with the symptoms of AIDS. AIDS patients have reported improved mood and appetite when using marijuana.  Gorter et al. report improved appetite and weight gain in patients taking dronabinol (synthetic THC).  Unfortunately, all studies of the effects of dronabinol have been in patients with advance symptomology.  "AIDS teach us that immuno-regulatory diseases are truly multi-factorial". . . and may be an ideal laboratory to investigate psychoimmunologic relationships, states Lydia  Temoshok, a member of the PNI laboratory started by Norman Cousins at UCLA.[54]       

          If marijuana improves mood and depression. it is probable that it has PNI effects.  A major reason for not necessarily wanting to separate its ability to make a person feel euphoric.  AIDS  provides a unique area for the development of a long term control matched study to look at the effects of marijuana on development of the transition for from HIV to full blown AIDS.    There are two separate lines of thinking for this study,  any drug that alters mood has potential benefits from a PNI point of view, but secondly and possibly even more importantly the discovery by Munro et al at University of Cambridge of a cannabinoid receptor in the macrophages in the marginal spleen,  suggests that THC may be capable of modulating immune function.[55]     

          Because AIDS patients suffer from a variety of problems including demylination, dementia, brain tumors, herpes and other viral infections, a long term controlled  study might lead to a understanding of marijuana effects on the immune system particularly if it effects the onset of any of the above conditions.  For instance, does marijuana reduce the number of AIDS patients who suffer from brain tumor or dymylination?  Whatever the case, further studies are justified, as marijuana most probably plays a role in modulation of the immune system.  These questions can only be answered after the establishment of a series of long term clinical studies.   

Post Traumatic Stress Disorder- Where the mind and body meet.

          Veterans from the Vietnam War have frequently reported that marijuana helps them manage PTSD, particularly the flashbacks associated with combat.  Psychologist familiar with treating PTSD are known to recommend the use of marijuana to their patients.   In an experiment at Massachusetts General Hospital conducted by the Harvard Psychology department veterans with PTSD  were shown pictures of the Vietnam war in order to stimulate the experience of 'flashback'.  Positron Emission Topography (PET) was used before and after each patient's session to determine which areas of the brain were most highly stimulated.  The hippocampus and the putamen were significantly more active during flashback, then other areas of the brain.  The activation of these particular areas of the brain are important for two reasons, first as we have demonstrated earlier these areas are clearly modulated by THC, secondly it suggests a mind/hippocampus/memory and body/putamen/muscle component to PTSD.  Could marijuana be involved in the regulation of memory in those veterans who find marijuana gives them symptomatic relieve.  While marijuana has been reported to effect short term memory, might it also play a role in the re-integration of traumatic memory in patients who have suffered emotional trauma.   

          Norbert Weiner, the father of information theory and the neuro-network approach to brain function believed that traumatic memory played a potential role in many types of mental disorders.  In his book,  Cybernetics: or Control and Communication in the Animal and the Machine,  he outlined a systems approach for understanding neurophysiology.  Weiner was one of the first scientists to recognize the importance of feedback in the nervous system stating,  "an excessive feedback is likely to be as serious a feedback to organized activity as a defective feedback."  He stated:

        We thus found a most significant confirmation of our hypothesis concerning the nature of at least some voluntary activity.  It will be noted that our point of view considerably transcended that current among neurophysiologists.  The central nervous system no longer appears as a self-regulated organ, receiving inputs from the senses and discharging into the muscles.  On the contrary, some of its most characteristic activities are explicable only as circular processes, emerging from the nervous system into the muscles, and re-entering the nervous system through the sense organ, whether they be proprioceptors or organs of the special senses.  This seems to us to mark a new step in the study of part of neurophysiology which concerns not solely the elementary process of nerves and synapses but the performance of the nervous system as a integrated whole.[56]

Recognizing the nervous system as one function unit, Weiner, went on to describe the statistical nature of the nervous function, and the importance of feedback mechanism for establishing homeostasis.   Control engineering and communication engineering were inseparable in Weiner's mind, because  problems centered not around techniques of electrical engineering, but around the notion of the message.  The message or mental state being a discrete or continuos sequence of measurements distributed in time- precisely called a time series by statisticians.[57]  Background noise, what you might compare to static on a radio station, altered the shape or meaning of a message, and distorted its original meaning.[58]  The degree of disorganization was related to entropy, while the  amount of information that could be processed was related to the organization of the entire nervous system.  Quite in opposition to the biological-behavioral approach to the value of mental states Weiner saw memory and its modulation as a potential factor in all mental disease.   Because Weiner's work is of such great importance in this area I will quote him at length.       

      Psychopathology has been rather a disappointment to the instinctive materialism of the doctors, who have taken the point of view that every disorder must be accompanied by material lesions of some specific tissue involved. ....These disorders (referring to schizophrenia, manic depression, and paranoia), we call functional, and this distinction seems to contravene the dogma of modern materialism that every- disorder in function has some physiological or anatomical basis in the tissues concerned. 

       This distinction between functional and organic disorders receives a great deal of light from the consideration of the computing machine. As we have already seen, it is not the empty physical structure or the computing machine that corresponds to the brain- to the adult brain at least- but the combination of this structure with the instructions given it at the beginning of a chain of operations and with all the additional information stored and gained from outside in the course of this chain. This information is stored in some physical form- in the form of memory- but part of it is in the form of circulating memories with a physical basis which vanishes when the machine is shut down or the brain dies, and part in the form  of

long-time memories, which are stored in a way  at which we can only guess, .....and even if we knew this, there is no way we can trace out the chain of neurons and synapses communicating with this, and determine the significance of this chain for the ideational content which it records.

       There is therefore nothing surprising in considering the functional mental disorders as fundamentally diseases of memory, of the circulating information kept by the brain in the active state, and of the long-time permeability of synapses. Even the grosser disorders such as paresis may produce a large part of their effects not so much by the destruction of tissue which they involve and the alteration of synaptic thresholds as by the secondary disturbances of traffic- the overload of what remains of the nervous system and the re-routing of messages-which must follow such primary injuries.

       In a system containing a large number of neurons, circular processes can hardly be stable for long periods of time. Either, as in the case of memories belonging to the specious present, they run their course, dissipate themselves, and die out, or they comprehend more and more neurons in their system, until they occupy an inordinate part of the neuron pool. This is what we should expect to be the case in the malignant worry which accompanies anxiety neuroses. In such a case, it is possible that the patient' simply does not have the room, the sufficient number of neurons, to carry out his normal processes of thought. Under such conditions, there may be less going on in the brain to load up the neurons not yet affected, so that they are all the more readily involved in the expanding process. Furthermore, the permanent memory becomes more and more deeply involved and the pathological process which occurred at first at the level of the circulating memories may repeat itself in a more intractable form at the level of the permanent memories. Thus what started as a relatively trivial and accidental reversal of stability may build itself up into a process totally destructive to the ordinary mental life.[59]

 Weiner's approach to memory and mental disorders is important for it recognizes the role that excessive or traumatic memory might play in all psycho pathological conditions.  PTSD is clearly one disorder in which memory becomes a problem of pathology.  The question arises as to whether we have the ability to clear those memories from the circuits that they occupy thereby creating more mental room for normal cognition. 

          It is my own work with several patients who suffered emotional trauma that marijuana a might be a bi-phasic pharmacological agent for memory.  In my experience one particular Vietnam veteran, I was surprised to see that at different dosages marijuana had quite different neurological effects.  At low doses combined with hypnosis it appear to facilitate the recall of traumatic memory, a recall of a traumatic event with an overall effect of lowering body tension, and improving affect.  A large dose appeared to block flashbacks.  This appears to be coincident with the hippocampus data which suggests that marijuana had a bi-phasic effect on the hippocampus.  How might this work neurologically?, and What does it tell us about the nature of endogenous ligand annadide?

          We know that cannabinoid receptors are plentiful in the two areas of which are activated during flashbacks.  One area the hippocampus regulates memory, the other motor control.  This is of extraordinary interest because it demonstrates that during the flashbacks, i.e. the evocation of Cannon's fight or flight response, mental events produce a corresponding preparation in the muscles, i.e. muscular modulation.  In other words there is a direct neurological connection between mind and body for conditions of psycho pathology. 

                   This mind (hippocampus) /body (putamen) approach to psychiatric disease is not a new one.   It was first introduced in 1933 by Wilhelm Reich, in his book, Character Analysis.  Originally a member of Freud's psychiatric circle at Vienna,  Reich began to notice that his patients who were psychologically  re-experiencing trauma were not always recovering from psychotherapy alone.  He observed that his patients were not only suffering mentally, but also from severe hardening of the neuro-musculature, which he described as body armoring.  He found that if he simultaneously treated the physical tension of the body, and the traumatic memories of the mind his patients recovered much more quickly.[60]

                   It has recently been reported that victims of physical and sexual abuse re-live the events when they get massage.  This adds another dimension to potential therapy, but suggests that the putamen, hippocampus activation during trauma may be circular in nature.  In other words, if you treat the body using massage to activate the putamen you get hippocampal activation, or changes that relate to the integration of traumatic memory, or if you alter hippocampus function through meditation or relaxation,  you can the same reaction.  It is clearly recognized that there is a one to one mapping of points in the brain to the body in the motor, somatosensory cortex, and the cerebellum, the question remains could the body be a physical representation of the mind?  An idea that is the foundation of Chinese medical theory.           This approach to trauma was recognized very early in Chinese medicine in a saying called Chua K'a.  It read as follows:

        The ancient Mongolian warriors called the Purified Bodies were without fear in their bodies.  To gain the natural state of courage, they studied fear, seeing.:

       1) we don't know our bodies.

       2) There are forbidden areas we never touch.  Why? Pain is stored there.  Why pain?

       The body is filled with little globules , all of which are blocked Kath (i.e. life energy, chi) This blocking is caused by pain which accumulates with time.  So every fear is retained in a globule with the memory of the pain which becomes a fear.  So in the body is the memory of all fears:  fear is the subjective history of pain in the body.[61] 

This is a reference to treating the physical tension of the body, as a means to stabilizing memory.  Only by further research will we be able to understand how treatment of physical body tension effects psychopathological conditions of memory.      

          Weiner speculated on the importance of his observations about memory for the practice of medicine.   He states:

  Note that a sharp frequency line is equivalent to an accurate lock. As the brain is in some sense a control and computation apparatus, it is natural to ask whether other forms of control and computation apparatus use clocks. In fact most of them do. Clocks, are employed in such apparatus for the purpose of gating. All such apparatus must combine a large number of impulses into single pulses. If these impulses are carried by merely switching the circuit on or off, the timing of the impulses is of small importance and gating is needed. However, the consequence of this method of carrying impulses is that an entire circuit is occupied until such time as the message is turned off; and this involves putting a large part of he apparatus out of action for an indefinite period. It is thus desirable in a computing or control apparatus that the messages be carried by a combined on-and-off signal. This immediately releases the apparatus for further use. In order for this to take place, the messages must be stored so that they can be released simultaneously, and combined while they are still on the machine. For this a gating is needed, and this gating can be conveniently carried out by the use of a clock.[62]

          Marijuana may prove to be the substance that helps in regulation of this gating mechanism.  Another clue to this process is that when gating mechanism are interrupted in Alzheimer patients whose behavior resembles a long regression back to childhood.  They lose bladder and bowel control and normal adult functioning while memories of childhood are sometimes quite clear.  Stress as been implicated as a factor in Alzheimer patients.  This disease represents a malfunction in the gating mechanisms of the hippocampus that is appears to be irreversible.  Because of the location of receptors in this area of the hippocampus, marijuana is a likely test canidate for testing its effects in the early stages of the disease.  Can marijuana help a certain type pf patient recover from chronic stress by readjusting the homeostasis between mind/body that malfunctions when the fight or flight response is repeatedly evoked?    

 Drug Addiction

          According to a National Institute of Drug Abuse study the cost of drug abuse soared to $144 Billion in 1988, an increase of almost 300% from the $46 billion estimated in 1980[63].  Today, all available statistics reflect a complete failure of drug policy, as the cost of drug abuse to society has steadily increased.  Over 520,000 deaths per year can be directly attributed to drug abuse according to the most recent government statistics,  419,000 of these directly related to tobacco addiction.[64]  66% of all crimes of violence are committed under the influence of alcohol.   In Massachusetts, a recent study by the Department of Corrections revealed that only 300 of the 10,000 who needed drug abuse treatment where getting it, and  85% of the prison inmates reported that drug abuse was a major factor in their involvement in crime.[65]

          Since Olds and Milner discovery of reward circuit in the brain in 1954, scientist have been trying to discover a pharmacological agent that is not physically addicting that might prove to be beneficial for the treatment of opium and heroin addiction.  Gardner et al. report that THC plays a role in the modulation of opiod receptors. and enhances medial forebrain bundle (MBF) electrical reward substrates, enhancing both basal and stimulated dopamine release. and the effects are blocked by naloxone. [66] Studies suggesting the effectiveness of marijuana in lowering narcotic abuse are not new. In 1868, The Indian Hemp Commission Report, an extensive study on the use of marijuana by the British government in India noted that people who used cannabis had a strong dislike for narcotics.[67]          Birch in 1889 noted that the immense value of marijuana is its immediate action in appeasing the appetite for opium, restoring the appetite for food, an increase in the heart's power, and to help induce sleep.[68]  Both the Chinese and Indian pharmacopoeia listed marijuana as a remedy of choice for narcotics addition.  Karen Model, Harvard Kennedy School of Government, reviewed statistics for emergency room episodes related to drug overdoses and found they were 12% lower in the states that had decriminalized marijuana.  She concluded that lowering the price of marijuana reduced the abuse of other substances.[69]

          In 1967 in Rome Harold Humes, a student of Norbert Weiner, demonstrated that combination of deep breathing exercises, marijuana, and massage appears to eliminate the withdrawal symptoms associated with long term opiate addiction.[70]  He described the technique in a 1979 lecture at University of Massachusetts at Amherst:

 ...We were trying to discover how to use a Chinese method.  You'll find in the Chinese medical textbooks that the specific remedy for chronic narcotics addiction is hashish.  But they don't tell you how to use it.  The hash alone won't do the trick.  Nor will the massage alone.  Rather the massage seems to potentate some neurological reaction which the massage triggers, to the net effect of a release...the patient actually jumps under your hands, and you can feel a bioelectrically charge released from a neuro-musculature hypertension.  these are followed by a sweat, sometimes a shout.  But you can see that the patient is immediately relieved  Narcotics addiction may be nothing more than the patient's failed attempt to treat an anxiety-tension level that has gone pathologically high.  He reduces it with the opiate, gets a few hours of relief, and then bang!-- chock a block up on his tension again.[71] 

          The following case history demonstrates some of the same therapeutic points earlier mentioned in the treatment of PTSD which also appear relevant in the treatment of drug addiction.

 It is the second day of abstinence form heroin. . . A couple of the members of the team have entered the room and stand or squat beside the mattress.  She barely appears to be breathing but she opens her eyes briefly.  Suddenly she draws a long quivering breath and begins to sob quietly, then more even and fuller.  A pallor even more intense than that of the addiction gives way to a flush.  She is sweating profusely.

He was doing some vibratory work on her when she started crying and hyperventilating.  After, laughter and sobs came in bubbles.  She said she had a memory of the accident, something she's blocked out of her memory. .  at least some of it. . . . when she opens her eyes and sees people hovering over her, she flashes back to the beginning of her addiction.  She is lying on the stretcher in the lights of the ambulance.  Her car is a total wreck and she is lucky to be alive.  The paramedics have anxiously.  There is nothing they can do for her shattered leg there on the highway, nothing but put her in the ambulance.  Nothing but morphine for the pain.

The patient sighs deeply.  Unexpectedly, she stands up and walks under her own power to the kitchen, where  she asks for a sandwich. 
She explains how she had turned to amphetamines after six months on morphine in the hospital, and then to heroin.  In the bedroom the senior member of the team explains that the return of appetite is a clear sign that the addiction is lifted.  As in this case, it often occurs after a major release, the recall of traumatic memory and the physical body tension associated with it.[72]

          Humes typically found that after a patient had relived a traumatic event or learned to release it,  his male patients frequently relived experiences of  abuse by a male parent.   While this is not to imply that drug addiction is not a multi-factorial problem, many authors have stated that fear of withdrawal is the main obstacle in getting people to stop using heroin.  Lindesmith states:

  "Addiction to opiates is determined by the individual's reaction to the withdrawal symptoms which occur when the drug's effects are beginning to wear off, rather than upon positive euphoric effects often erroneously attributed to its continued use. The more specifically, the complex of attitudes which constitute addiction is built up in the process of conscious use of the drug to alleviate or avoid withdrawal distress. This theory, though simple in form, has considerable explanatory value, and offers a means of accounting for varied and paradoxical aspects of the habit, such as the addict's claim that he feels normal under the drug's influence, as well as his tendency to increase the dose to a point where its use becomes much more unpleasant and burdensome than it need be. The hypothesis presented makes intelligible the constant preoccupation of the addict with the drug, and explains how the unpleasant and unwelcome appellation 'dope fiend' is forced upon him.[73]

A method of painless detoxification could go a long way in helping prevent what appears to be the start of a major heroin epidemic.  Between 1992 and 1993 the number of emergency room visits for heroin related overdose rose from 21,400 to 30,800, an increase of 44%.[74]

          An important consideration for using marijuana is this type of application is whether it will lead to the same abstinence syndrome after it is discontinued.  All medical authorities agree on one point, marijuana is not physically addictive.  Westlake et al. demonstrated that chronic exposure to 5, 10, 20, mg of THC/kg, did not appear to alter the striatum, cerebral cortex, cerebellum, hippocampus, and brainstem/spinal chord in the rat or monkey.[75]

The Current State of Research

                    It has been estimated that there are as many as 1,000,000,000^25 circuits in the human brain, after 50 years of research we still no very little about the how it works.  It may take 100 more years of research to understand the biological imbalances of the brain.   Marijuana may provide one of the unique tools for these investigations, but no investigation are possible until it is permanently returned to the pharmacopoeia.  This is a logical first step in correcting a mistake that was made in 1937.  A review of the money being spent on research involving THC and CBD reveal that more than enough research has been done on animals with these substances, and it is now time to begin comprehensive studies of the use of marijuana in a variety of medical conditions.  The cost effectiveness of marijuana as medicine more than justify the financial outlay that would be necessary by the NIH to start such research projects.  With the health of many patients in mind, the time to act is now.  Mistakes don't get better with age.  Research experiments with marijuana may help us answer a question that is as old as science itself;  How do diseases of memory effect the body?

Last modified: 09/05/08