Neurochemistry and marijuana

Discussion in 'Cannabis' started by bewilderment, Jul 8, 2006.

  1. bewilderment

    bewilderment Drug Geek Extraordinaire Platinum Member & Advisor

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    I recently got into a bit of a debate about the neurochemistry of marijuana. Someone was asking if smoking pot would affect her SSRI. Someone replied that marijuana causes depression so it may cancel it out, to which I replied with what I knew which was this:

    where did you hear that pot makes you depressed? Perhaps amotivational syndrome could be a little depressing. But, marijuana doesn't affect the neurotransmitters (serotonine, dopamine, and norepinephrine) which are said to cause depression when the brain doesn't have enough of those happy little molecules firing back and forth, but instead it works on the cannabinoid receptors. Actually, cannabis is thought to have anti-depressant and anti-anxiety properties.

    Weed enhances all the functionings of the cannabinoid network. The primary functions of the cannabinoid network are believed to be regulating the immune cells and the sleep/wake cycle. There are lots of natural cannibinoids (as opposed to synthetic and endogenous) but the most common ones (and the ones present in marijuana) are: tetrahydrocannabinol (THC), cannabidiol (CBD) and cannabinol (CBN). There are two known cannibinoid receptors: CB1 an CB2.

    THC appears to moderate pain and to be neuroprotective and has a greater affinity for the CB1 receptors than for the CB2 receptors. Its effects are mostly cerebral. CBD seems to moderate the euphoric effects of THC and it appears to relieve convulsion, inflammation, anxiety, and nausea. CBD has a greater affinity for the CB2 receptor than for the CB1 receptor. It is thought to have more effect on the body. CBN is the primary product of THC degradation, and there is usually little of it in a fresh marijuana plant. CBN content increases as THC degrades in storage, and with exposure to light and air. It is only mildly psychoactive, and is perceived to be sedative or stupefying.

    Marijuana actually works as a stimulant and depressant as far as the central nervous system is concerned and that isn't related to depression. Rather, marijuana balances the autonomic nervous system (ANS) by its sedative / stimulant qualities which take place by its action on the hypothalamus part of the brain (the place from whence the autonomic system receives its instructions). The ANS is that part of our system which is responsible for all non-voluntary activity of the body / mind, such as rate of heart beat, size of pupils, rate of breath, chemical mixes in body fluids, etc.

    Stimulant effects of marijuana include an increase in pulse rate, blood pressure, and heartbeat. Some of the depressant effects are: relaxation, stress reduction, slowness, lethargy.

    Sorry, I didn't mean to turn this into some sort of lecture or something. I was just bored this morning and mainly decided to put this together as information for myself.
    ---

    To which she replied that it was in psychology textbooks that marijuana is said to decrease serotonin. I searched the net for more info on this, but many sites say different things: Some sites say that marijuana is a bit of an SSRI (this is probably why one would get depressed when quitting marijuana after long-term use I believe, that or it's just a case of the blues and learning to live sober), some sites say that it lowers serotonin, and some say that it has no effect whatsoever. I was wrong in saying that marijuana doesn't affect neurotransmitters, but the only neurotransmitters that I can find much reliable information about how cannabis affects the brain is some of the GABA receptors and of course anandamide.

    Does anyone know more about how cannabis affects other neurotransmitters such as serotonin and provide a legitimate unbiased source. I can't seem to find any good info.
     
  2. psyche

    psyche Palladium Member

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    Good post, altough cannabis lowers blood pressure instead of increasing it.

    My hunch would be the latter. Long-term use of SSRIs is supposed to relieve anxiety, and only long term. It propably raises serotonin levels(meaning there is more serotonin bond to receptors, in this case because of an increase in number of serotoninreceptors).

    As for the sources or more info: I have no idea whatsoever.
     
  3. Decoy DeVille

    Decoy DeVille Newbie

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    Actually Cannabis does raise your blood pressure.. not reduce it!


     
  4. psyche

    psyche Palladium Member

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    Actually, according to wikipedia:
    "Lower blood pressure while standing. Higher blood pressure while sitting"

    And according to whirlwind:

    "The short-term effect of marijuana will increase blood pressure and pulse rate up to 16 points above normal. It will also slow down the digestive processing of food. People who smoke marijuana often will have a below normal pulse rate and blood pressure"

    Other source only says: "Cannabis affects blood pressure and increases heart rate."

    Erowid states: "lightheadedness or fainting (in cases of lowered blood pressure)"

    So what do you guys with shitloads of those respectable green boxes say? I always thought that it would lower it because I always almost faint if I rise up fast. Could be blood sugar levels too. How does cannabis affect them?
     
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  5. hh339

    hh339 Gold Member

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    Maybe it depends on whether it is sativa or indica + the amount smoked. I say he felt like his pulse was speeding mildly when he smoked pure sativa in high amounts, while indica made him very calm, almost too calm, and probably lowered his pulse.
     
  6. bewilderment

    bewilderment Drug Geek Extraordinaire Platinum Member & Advisor

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    Well, I don't know about the faint feeling. Often when I take ephedrine, I get a faint feeling when I stand up, the room spins for a minute yet I know that ephedrine raises blood pressure. But, people's blood pressure and such seem to change while sitting, standing, etc without any substances anyway. Also, swim's wife was having fainting spells when she was using drugs that are definately stimulants such as meth. She also usually doesn't like to lie down when she's feeling faint because she says that it makes her feel like her heart's speeding up, probably because of the change of blood flow and the heart compensating. Swim says that her pulse usually feels sped up depending upon how much she has been smoking. If her tolerance has gone up then sometimes she notices no effect on her pulse.

    See, so much conflicting info!
     
  7. psyche

    psyche Palladium Member

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    That's definately true, but it doesn't mean your blood pressure is up.
     
  8. bewilderment

    bewilderment Drug Geek Extraordinaire Platinum Member & Advisor

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    Can one tell if they're blood pressure is high or low without actually measuring it?

    Edit: also, This is from wikipedia: "Sometimes the blood pressure drops significantly when a patient stands up from sitting. This is known as orthostatic hypotension; gravity reduces the rate of blood return from the body veins below the heart back to the heart, thus reducing stroke volume and cardiac output.

    When people are healthy, they quickly constrict the veins below the heart and increase their heart rate to minimize and compensate for the gravity effect. This is carried out involuntarily by the autonomic nervous system. The system usually requires a few seconds to fully adjust and if the compensations are too slow or inadequate, the individual will suffer reduced blood flow to the brain, dizziness and potential blackout. Increases in G-loading, such as routinely experienced by supersonic jet pilots "pulling Gs", greatly increases this effect. Repositioning the body perpendicular to gravity largely eliminates the problem."

    And I also found and abstract of a general article here: http://www.erowid.org/plants/cannab...-sci_1/1993_mathew_life-sci_1_abstract.shtml:

    "In experienced marijuana smokers, marijuana smoking was accompanied
    by a significant bilateral increase in cerebral blood flow (CBF)
    especially in the frontal regions and cerebral blood velocity. The
    post-marijuana CBF increase could not be explained on the basis on
    changes in general circulation or respiration. Similarly, the CBF
    increase was unrelated to plasma levels of tetrahydrocannabinol and
    extracranial circulation. Behavioral changes showed significant
    correlations with CBF. CBF and brain function are closely coupled and
    therefore it seemed highly likely that CBF changes after marijuana were
    closely related to its effect on mood and behavior."

    So, all of this doesn't explain what effects cannabis has on blood pressure, but this may explain feeling faint. Many things which increase cerebral blood flow (I've noticed even ginseng causes me to feel faint when I stand up suddenly) will make you feel faint when you change positions.
     
    Last edited: Jul 8, 2006
  9. bewilderment

    bewilderment Drug Geek Extraordinaire Platinum Member & Advisor

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    I have found that I was probably wrong with saying that it definately doesn't affect the neurotransmitters associated with depression, but still haven't seen anything to say anything about it causing depression and how (although I have heard people say this before). I still can't find anything about how serotonin is affected so if anyone wants to help out then please do.

    I have found this about how marijuana affects norepinephrine:

    "Memory effects

    One of the primary effects of marijuana in humans is disruption of short-term memory.68 That is consistent with the abundance of CB1 receptors in the hippocampus, the brain region most closely associated with memory. The effects of THC resemble a temporary hippocampal lesion.63 Deadwyler and colleagues have demonstrated that cannabinoids decrease neuronal activity in the hippocampus and its inputs 23, 24, 83 In vitro, several cannabinoid ligands and endogenous cannabinoids can block the cellular processes associated with memory formation.29, 30, 116, 157, 163 Furthermore, cannabinoid agonists inhibit release of several neurotransmitters: acetylcholine from the hippocampus,49,50,51 norepinephrine from human and guinea pig (but not rat or mouse) hippocampal slices,143 and glutamate in cultured hippocampal cells.144 Cholinergic and noradrenergic neurons project into the hippocampus, but circuits within the hippocampus are glutamatergic.f Thus, cannabinoids could block transmission both into and within the hippocampus by blocking presynaptic neurotransmitter release."

    Then another section suggests that it may increase dopamine:

    "Reward and dependence

    Experimental animals that are given the opportunity to self-administer cannabinoids generally do not choose to do so, which has led to the conclusion that they are not reinforcing and rewarding.38 However, behavioral95 and brain stimulation94 studies have shown that THC can be rewarding to animals. The behavioral study used a "place-preference" test, in which an animal is given repeated doses of a drug in one place, and is then given a choice between a place where it did not receive the drug and one where it did; the animals chose the place where they received the THC. These rewarding effects are highly dose-dependent. In all models studied, cannabinoids are only rewarding at mid-range; doses that are too low are not rewarding, doses that are too high can be aversive. Mice will self-administer the cannabinoid agonist, WIN 55,212, but only at low doses.106 This effect is specifically mediated by CB1 receptors, and indicates that stimulation of those receptors is rewarding to the mice. Antagonism of cannabinoid receptors is also rewarding in rats; in conditioned place-preference tests, animals show a preference for the place they receive the cannabinoid antagonist, SR141716A, at both low and high doses.140 Cannabinoids increase dopamine levels in the mesolimbic dopamine system of rats, a pathway associated with reinforcement.25, 39, 161 However, the

    2.32

    mechanism by which THC increases dopamine levels appears to be different from that of other abused drugs....These increases in dopamine are due to increases in the firing rate of dopamine cells in the ventral tegmental area by 9-THC47. However, these increases in firing rate in the ventral tegmental area could not be explained by increases in the firing of the A10 dopamine cell group, where other abused drugs have been shown to act51."

    From: http://www.rism.org/isg/dlp/ganja/analyses/Marijuana and Medicine 2b.html
     
  10. psyche

    psyche Palladium Member

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    Yep, VTA not being involved explains why cannabis has so low addiction potential. At first I thought cannabis is mere psychedelic and it binds to serotonin 2A/C receptors like all others, so I've subconciously thought to this point that cannabis affects mostly to the serotonin levels. That doesn't seem to be the case:

    "Experiments have shown that THC can affect two neurotransmitters: norepinephrine and dopamine. Serotonin and GABA levels may also be altered."

    from http://faculty.washington.edu/chudler/mari.html
     
  11. bewilderment

    bewilderment Drug Geek Extraordinaire Platinum Member & Advisor

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    That site's not bad, I had skipped over it earlier when it popped up on a search since it is after all titled "neuroscience for kids". It still doesn't say through what mechanism the neurotransmitters are affected nor does it say whether it raises or lowers serotonin or what.

    I think the discussion that I was having on another forum kind of died because people there really don't seem to be into the science of things as much as people here so I never got a reply from the person who suggested that marijuana affects serotonin and thus causes depression. So far, I don't see much of how marijuana could cause depression except that after use, one may feel a little down because they're used to having more dopamine in their brains (and perhaps serotonin). It could also maybe make someone a little depressed in that it lowers norepinephrine, but I think that would mostly just calm a person down unless their dopamine and/or serotonin was being being lowered as well...but that's speculation on my part.
     
  12. psyche

    psyche Palladium Member

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    Ok, here's from The psychopharmacology of herbal medicines by Marcello Spinella:

    "Neuropharmacological effects of THC:
    Cannabinoid - Activation of cannabinoid (CB) receptors
    Amino acids - Reduces AMPA/kainate activity
    Acetylcholine - Inhibition of ACh release (biphasic)
    Monoamines - Activates mesolimbic DA
    Increases NE turnover
    Opioids - Synergistic effect
    Neuroendocrine - Reduces testicular production of testosterone, Enhances target responsivity to gonadotropins, reduces LH and prolactin secretion, Increases adrenocorticotrophic hormone levels, increases corticosterone levels
    Eicosanoids - Inhibition of PHE and PGF"

    As you can see, this book covers all the possible systems given substance affects, not only the primary ones. So THC stimulates the presynaptic activity of mesolimbic dopaminergic neurons, wich is mediated through CB1-receptors. THC increases the firing rate and burst-pattern firing in the ventral tegmental area and substantia nigra, although the VTA is more sensitive in this respect. Both of those are linked with reinforcement and addiction, but I guess that THC isn't addicting because it doesn't directly act to dopamine receptors. Hope someone got a better idea on this one?

    And yes, cannabinoids also induce increases in norepinephrine in the prefrontal cortex, but doesn't seem to have any effect to 5-HT.

    If you are into detailed neuropharmakology, this book will give you all the details you'll need. Altough I had hard time reading it, it was worth it. And it serves as a good source, too. Well, that's the only book on field of pharmacology so I don't have anything to compare. I'll see how does the Biochemical basis of neuropharmacology compare when it arrives.
     
    Last edited: Jul 10, 2006
  13. Forthesevenlakes

    Forthesevenlakes Platinum Member

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    This quote is from the link bewilderment posted:

    "Cannabinoids clearly affect movement in rodents, but the effects depend on the dose: low doses stimulate and higher doses inhibit locomotion."

    Now, I need to do more reading on the topic to say for sure, but could low doses perhaps be used to facilitate the ease of movement in patients with Parkinson's? Thoughts on this, anyone?
     
  14. bewilderment

    bewilderment Drug Geek Extraordinaire Platinum Member & Advisor

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    I've been reading through many more articles about this and wondered why I didn't use Pubmed before (lots of interesting drug-related articles there but also a pain to browse through to find free text) anyway I've found lots of studies and theories concerning Parkinson's. Actually marijuana seems much more promising as a treatment for MS than Parkinson's, supposedly.

    It also seems that the studies involving movement in rodents were taken from two articles which I can only find the abstract on, but here's the abstract of each of the studies:

    "Effects of the endogenous cannabimimetic anandamide were assessed over a wide dose range in a series of physiological and behavioral assays. These included the tetrad of tests in mice commonly used to assess cannabinoid-induced effects (motor activity, ring catalepsy, hypothermia, and analgesia tests), as well as a model for agonistic behavior on dyadic interactions of singly housed males with nonaggressive group-housed partners. Anandamide-induced effects on leukocyte phagocytosis were measured in a chemiluminescence assay. Results indicated that the higher doses tested (10-100 mg/kg) produced the well-known inhibitory effects in all of the above parameters as well as inhibition of phagocytosis. The lowest dose of anandamide tested (0.01 mg/kg) stimulated behavioral activities in the open field, on the ring and aggressive behavior in timid singly housed mice. This dose of 0.01 mg/kg, also stimulated phagocytosis. We suggest several possible mechanisms to explain these findings such as a differential involvement of a Gs and a Gi protein activated at low and high doses, respectively, allosteric modulation of the cannabinoid, and activation of presynaptic cannabinoid receptors by low doses of anandamide."

    From: http://www.ncbi.nlm.nih.gov/entrez/...ve&db=PubMed&list_uids=9476980&dopt=Citation

    And:

    "The effects of the cannabinoid receptor agonist WIN 55,212-2 on endogenous extracellular glutamate levels in the prefrontal cortex of the awake rat and in primary cultures of rat cerebral cortex neurons were investigated. In the prefrontal cortex WIN 55,212-2 (0.1 and 1 mg/kg i.p.) increased dialysate glutamate levels from of the awake rat, while the lower (0.01 mg/kg) and the higher (2 mg/kg) doses were ineffective. Furthermore, the WIN 55,212-2 (0.1 mg/kg)- induced increase of dialysate glutamate levels was counteracted by pretreatment with the selective CB1 receptor antagonist SR141716A (0.1 mg/kg i.p.) and by the local perfusion with a low-calcium Ringer solution (Ca2+ 0.2 mM). In primary cultures of rat cerebral cortex neurons, WIN 55,212-2 (0.01–100 nM) increased extracellular glutamate levels, displaying a bell-shaped concentration–response curve. The facilitatory effect of WIN 55,212-2 (1 nM) was fully counteracted by SR141716A (10 nM), by the replacement of the normal Krebs Ringer-bicarbonate buffer with a low Ca2+ medium (0.2 mM) and by the IP3 receptor antagonist xestospongin C (1 µM). These in vivo and in vitro findings suggest an increase in cortical glutamatergic transmission by CB1 receptors, an effect that may underlie some of the psychoactive and behavioural actions of acute exposure to marijuana."

    http://cercor.oxfordjournals.org/cgi/content/abstract/11/8/728

    So, they were not using cannibinoids actually found in cannabis.

    If they were to use naturally occuring exogenous cannibinoids then they could curb the anxiety induced my THC with the other cannibinoid CBD which is associated with the ant-anxiety properties of marijuana. In fact, a treatment for MS is underway involving CBD and THC. This could explain why some marijuana will make one more prone towards paranoia while other cannabis will not, it's dependent upun THC:CBD ratios among other things:

    "One double-blind study of eight volunteers reported that CBD can block the anxiety induced by high doses of THC (0.5 mg/kg).177 There are numerous anecdotal reports claiming that marijuana with relatively higher ratios of THC:CBD is less likely to induce anxiety in the user than marijuana with low THC:CBD ratios; but, taken together, the results published thus far are inconclusive.

    "The most important effect of CBD seems to be its interference with drug metabolism, including 9-THC metabolism in the liver.14,114 It exerts that effect by inactivating cytochrome P450s, which are the most important class of enzymes that metabolize drugs. Like many P450 inactivators, CBD can also induce P450s after repeated doses.13 Experiments in which mice were treated with CBD followed by THC showed that CBD treatment was associated with a substantial increase in brain concentrations of THC and its major metabolites, most likely because it decreased the rate of clearance of THC from the body.15"

    " CB1 and CB2 are similar, but not as similar as members of many other receptor families are to each other. On the basis of a comparison of the sequence of amino acids that make up the receptor protein, the similarity of the CB1 and CB2 receptors is 44% (Figure 2.2). The differences between the two receptors indicate that it should be possible to design therapeutic drugs that would act only on one or the other receptor and thus would activate or attenuate (block) the appropriate cannabinoid receptors. This offers a powerful method for producing biologically selective effects. In spite of the difference between the receptor subtypes, most cannabinoid compounds bind with similar affinity2 to both CB1 and CB2 receptors. One exception is the plant-derived compound CBD, which appears to have greater binding affinity for CB2 than for CB1"

    and furthermore, regarding Parkinson's and other disorders:

    ""Cannabinoid receptors are particularly abundant in some areas of the brain. The normal biology and behavior associated with these brain areas are consistent with the behavioral effects produced by cannabinoids (Table 2.5 and Figure 2.5). The highest receptor density is found in cells of the basal ganglia that project locally and to other brain regions. These cells include the substantia nigra pars reticulata, entopeduncular nucleus, and globus pallidus, regions that are generally involved in coordinating body movements. Patients with Parkinson's or Huntington's disease tend to have impaired functions in these regions."

    "Cannabinoids tend to inhibit neurotransmission, although the results are somewhat variable. In some cases, cannabinoids diminish the effects of the inhibitory neurotransmitter, g-aminobutyric acid (GABA);144 in other cases, cannabinoids can augment the effects of GABA.120 The effect of activating a receptor depends on where it is found on the neuron: if cannabinoid receptors are presynaptic (on the "sending" side of the synapse) and inhibit the release of GABA, cannabinoids would diminish GABA effects; the net effect would be stimulation. However, if cannabinoid receptors are postsynaptic (on the "receiving" side of the synapse) and on the same cell as GABA receptors, they will probably mimic the effects of GABA; in that case, the net effect would be inhibition."


    These exerpts all taken from this page: http://newton.nap.edu/html/marimed/ch2.html#TEXT_REF111
    which is an online version of the book "Medicine and Marijuana"and unbeknownst to me, the page I referenced before was an exerpt of. It has a section on regarding marijuana and movement disorders which states:

    "Parkinson's disease, a degenerative disease, affects about 1 million Americans over the age of 50.53 It is characterized by bradykinesia (slowness in movement), akinesia (abrupt stoppage of movement), resting tremor, muscular rigidity, and postural instability.

    Theoretically, cannabinoids could be useful for treating Parkinson's disease patients because cannabinoid agonists specifically inhibit the pathways between the subthalamic nucleus and substantia nigra and probably also the pathways between the subthalamic nucleus and globus pallidus (these structures shown in Figure 2.6).165,169 The latter effect was not directly tested but is consistent with what is known about these neural pathways. Hyperactivity of the subthalamic neurons, observed in both Parkinson's patients and animal models of Parkinson's disease, is hypothesized to be a major factor in the debilitating bradykinesia associated with the disease.36 Furthermore, although cannabinoids oppose the actions of dopamine in intact rats, they augment dopamine activation of movement in an animal model of Parkinson's disease. This suggests the potential for adjunctive therapy with cannabinoid agonists.165—167,169

    At the time of this writing, we could find only one published clinical trial of marijuana involving five cases of idiopathic Parkinson's disease.48 That trial was prompted by a patient's report that smoking marijuana reduced tremor, but the investigators found no improvement in tremor after the five patients smoked marijuana--whereas all subjects benefited from the administration of standard medications for Parkinson's disease (levodopa and apomorphine).48 Although new animal data might someday indicate a use for cannabinoids in treating Parkinson's disease, current data do not recommend clinical trials of cannabinoids in patients with Parkinson's disease. "

    Movement disorders "The abundance of CB1 receptors in basal ganglia and reports of animal studies showing the involvement of cannabinoids in the control of movement suggest that cannabinoids would be useful in treating movement disorders in humans. Marijuana or CB1 receptor agonists might provide symptomatic relief of chorea, dystonia, some aspects of parkinsonism, and tics. However, clinical evidence is largely anecdotal; there have been no well-controlled studies of adequate numbers of patients. Furthermore, nonspecific effects might confound interpretation of results of studies. For example, the anxiolytic effects of cannabinoids might make patients feel that their condition is improved, despite the absence of measurable change in their condition.

    Compared to the abundance of anecdotal reports concerning the beneficial effects of marijuana on muscle spasticity, there are relatively few claims that marijuana is useful for treating movement disorders. This might reflect a lack of effect or a lack of individuals with movement disorders who have tried marijuana. In any case, while there are a few isolated reports of individuals with movement disorders who report a benefit from marijuana, there are no published surveys indicating that a substantial percentage of patients with movement disorders find relief from marijuana. Existing studies involve too few patients from which to draw conclusions. The most promising reports involve symptomatic treatment of spasticity. If the reported neuroprotective effects of cannabinoids discussed in chapter 2 prove to be therapeutically useful, this could benefit patients with movement disorders, but without further data such a benefit is highly speculative. Since stress often transiently exacerbates movement disorders, it is reasonable to hypothesize that the anxiolytic effects of marijuana or cannabinoids might be beneficial to some patients with movement disorders. However, chronic marijuana smoking is a health risk that could increase the burden of chronic conditions, such as movement disorders.

    Cannabinoids inhibit both major excitatory and inhibitory inputs to the basal ganglia. This suggests that a cannabinoid agonist could produce opposite effects on movement, depending on the type of transmission (excitatory or inhibitory) that is most active at the time of drug administration. This property could be used to design treatments in basal ganglia movement disorders, such as Parkinson's disease where either the excitatory subthalamic input becomes hyperactive or the inhibitory striatal input becomes hypoactive. The dose employed would be a major factor in the therapeutic uses of cannabinoids in movement disorders; low doses should be desirable, while higher doses could be expected to aggravate pathological conditions. Thus, there is a clear reason to recommend pre-clinical studies; that is, animal studies to test the hypothesis that cannabinoids play an important role in movement disorders.

    With the possible exception of multiple sclerosis, the evidence to recommend clinical trials of cannabinoids in movement disorders is relatively weak. Ideally, clinical studies would follow animal research that provided stronger evidence than is currently available on the potential therapeutic value of cannabinoids in the treatment of movement disorders. Unfortunately, there are no good animal models for these disorders. Thus, double-blind, placebo-controlled clinical trials of isolated cannabinoids that include controls for relevant side effects should be conducted. Such effects include anxiolytic and sedative effects, which might either mask or contribute to the potential therapeutic effects of cannabinoids. "

    "Cannabinoid's major effect on movement is hypoactivity. Nevertheless, a biphasic excitatory/inhibitory effect of cannabinoids on movement has been repeatedly acknowledged. However, the literature is lacking a detailed description of such an effect. In this study, we performed a dose-response study of the effects of Delta(9)-tetrahydrocannabinol on movement. Immediately after the administration of vehicle or a dose of Delta(9)-tetrahydrocannabinol (0.2, 0.5, 1, 1.5, 2, 2.5, 3, 4, or 5 mg/kg), the animal was placed in an activity monitor and observed for 1 h. Several parameters were recorded. The horizontal and vertical activities were measured as the number of photobeams broken between the photocells on the walls of an activity monitor. The number of wet dog shakes, scratches with hindpaw, mouth movements, forepaw flutters were also recorded, as was the amount of time in minutes that each subject spent grooming. The number of fecal boluses was recorded as an index of autonomic activity. Each animal was subsequently tested for catalepsy in the bar test. A triphasic effect was observed: low doses of the cannabinoid receptor agonist Delta(9)-tetrahydrocannabinol (0.2 mg/kg) decreased locomotor activity while higher doses (1-2 mg/kg) dose-dependently stimulated movement until catalepsy emerged (2.5 mg/kg) accompanied by decreases in activity."


    So, there you have it. I still believe that marijuana would be beneficial in small doses of where there is a high THC:CBD ratio, but still there are the risks of stimulation. I'm sure that there is something in this wonderful plant that would help push treatment research in the right direction, however, as it stands it is quite difficult to do research on medical marijuana. Remember the ruling a couple months back that marijuana has no medicinal value? Newscientist had a brief article:

    "It's enough to make your head spin. The US Food and Drug Administration announced on Friday that marijuana is not a legitimate medicine because there is no hard evidence to show its safety or effectiveness. But marijuana researchers argue political obstacles make it almost impossible to get such data.

    The FDA says it was responding to requests for an opinion on the drug's medical worth by Mark Souder, the Indiana congressman who opposes marijuana in medicine as well as in foreign fields (see above). The FDA's statement contradicts a 1999 report by the US Institute of Medicine (IOM) suggesting that marijuana had the potential to treat pain, nausea and anorexia. Since then 11 US states have legalised the medicinal use of marijuana, even though possession of the drug is still a federal crime.

    Stanley Watson, a co-chair of the IOM review, agreed with the FDA that no studies of medical marijuana have been done that meet FDA standards. However, a large amount of anecdotal evidence suggests that marijuana is a promising treatment. "It doesn't upset me to hear them say this," he says. "I just think they should do the studies."

    Donald Abrams, a marijuana researcher from the University of California, San Francisco, agrees. He says that lack of funding and regulatory obstacles make pursuing the research extremely difficult. "There aren't many people willing to jump all the hurdles," he says."

    http://www.newscientist.com/channel...00-medical-marijuana-suffers-knock-in-us.html

    Sad really. Also, all of that being said, I found another excellent source which is a very lengthy articled entitled "Cannabis and the brain" which explores many interesting aspects of marijuana pharmacology and is found here: http://brain.oxfordjournals.org/cgi/content/full/126/6/1252