Please Scroll Down to See Forums Below 
serge
New member
original on anabolicextreme.com
i cut some parts out, to make it a bit easier to read
THC Unbound
by Grendel
THC Pharmacology
THC, as found in marijuana is usually smoked but can be eaten. THC can also be injected intravenously. Peak plasma levels are reached ten minutes after smoking. The psychoactive components are effective for two to three hours, however THC has a long half-life due to its lipid soluble nature and redistribution into fatty tissue. THC can be detected in urine months after initial administration. THC is metabolized through the cytochrome P450 system. Approximately one third is eliminated renally and two-thirds through fecal excretion. The LD-50 (lethal dose for 50 percent of those administered that amount of the drug) is 1270mg/kg in male rats and 730mg/kg in female rats (when taken orally in sesame oil). The LD-50 from inhalation is 42mg/kg in rats [6]. Generally speaking, it would be almost impossible for a human to overdose on THC.
THC and Sex Hormones
For the athlete and bodybuilder, hormones are extremely important. Testosterone, the male sex hormone, is responsible for muscle growth, strength, and body composition. Synthetic testosterone, and its derivate anabolic steroid relatives, are used to enhance athletic performance and used, aesthetically, by bodybuilders to develop larger stronger muscles. Even for athletes who do not use performance enhancing anabolic hormones, it is extremely important to keep natural product of sex hormones at the right levels if not slightly elevated through proper diet, training, and nutrition. Therefore, any serious athlete should investigate the impact of any chemical on their endogenous hormone product.
The traditional standpoint is that THC negatively impacts the hormonal profile of users, specifically decreases the amount of testosterone produced by the body, increasing estrogen levels in men, and reducing sperm motility (fertility). These findings are typically based on tests on animals, extrapolated to apply to humans. However, the scientific findings are hardly conclusive and, in fact, seem to dispute the hypothesis that THC has any negative impact on human hormone levels.
A study by at the University of Iowa, in 1991, disputed that common belief that THC affected the levels of testosterone and other sex hormones in the human body. The study was a direct contradiction of the 1974 study, by Dr. R.C. Kolodny, which reported a decrease in testosterone levels in men who smoked marijuana regularly and helped found the common belief that THC was responsible for feminizing effects on men. The University of Iowa study found that chronic marijuana use had no effect on testosterone, luteinizing hormone, and follicle stimulating hormone, prolactin and cortisol in men or women. The study also noted that six other studies has failed to show lower testosterone, leading the Iowa study to conclude that “it appears that marijuana, even heavy use of the kind that is typical in the United States, doesn’t alter testosterone levels.” However, the study did caution that heavy prolonged use might have other adverse effects, including “possible effects on reproductive function and mild, selective cognitive impairments associated with heavy, chronic use.” [18]
A 1994 study found that THC probably does disrupt the male and female reproductive system and hormones, at least in animals. The study found a reduction in the secretion of testosterone and therefore reduced sperm production, viability, and motility in human males; this means that male fertility was negatively impacted. The study did admit that it was unclear whether this data could be applied to humans and recognized that cannabinoids have both negative and positive effects on testosterone levels in humans. One of the study’s authors postulated that the impact of THC on grown human males would be minimal, but that the impact would be more profound on pre-pubescent males. [19]
A 1997 study showed that THC, administered in large dosages on animals, does seem to affect sex hormone levels. However the effects vary from one study to the next and when effects do occur, they are temporary and highly dependent on dosage and timing of the THC administration. The study concluded that it was possible that THC might cause infertility in men with already low sperm counts, but that it was unlikely to effect healthy subjects. Additionally, the study stated that users develop a tolerance to any hormonal effects of THC. The study concluded that THC has neither a feminizing effect in males nor a masculinizing effect in females [20].
But a 1998 study showed that cannabinoids, in animals, caused alterations in both male and female sexual hormones but there was no evidence that THC adversely effected human fertility of caused any chromosomal or genetic damage as some critics postulated that THC would do [21].A 2001 study concluded that cannabis smoking decreased the blood levels of three hormones; luteinizing hormone (LH), follicle stimulating hormone (FSH), and testosterone. The study also found a lower sperm count in men who were reported heavy marijuana smokers. But other studies did not measurable differences in men who were light or heavy users of THC. Acute THC treatment did produce a consistent and significant dose- and time-related decrease in LH and testosterone in male rodents; and in male rhesus monkeys an acute dose of THC produced a 65% reducing in blood testosterone levels within 60 minutes of treatment and lasting for approximately 24 hours [22].
The general conclusion seems to be that even heavy use of THC in all its forms has little impact on health human hormone levels. If there are any effects, they appear to be short lived and dosage dependent. It seems unlikely that an advanced athlete would be harmed by occasional use of THC for other purposes, particularly the stimulation of appetite.
THC and Leptin: The Weight loss and Appetite Link
A brief overview of Leptin
There are several breeds of laboratory mice that have a single-gene mutation that causes them to become extremely fat, clinically obese. These mice fall into two classes; mice with the genotype ob/ob which involves a mutation in the gene for the protein hormone leptin and db/db which involve mutations in the gene that encoded the receptor for the hormone leptin. When ob/ob mice are treated with injections of leptin they lose their fat and return to a healthy normal body weight.
Leptin is manufactured in fat cells or adipose tissue and circulating levels of leptin are directly linked to overall fat content of the body. Leptin acts on receptors in the hypothalamus of the brain where leptin:
• Counteracts the effects of neuropeptide Y (a potent feeding stimulant secreted by cells in the gut and in the hypothalamus);
• Counteracts the effects of anadamide (another potent feeding stimulant that binds to the same receptors as THC, the active ingredient of marijuana)
• Promotes the effects of alpha-MSH, an appetite suppressant;
The result is the inhibition of food intake. Thus leptin provides homeostatic control of food intake. It is the absence of a function hormone or its corresponding receptor that leads to uncontrolled food intake and resulting obesity. In addition to effecting the hypothalamus, leptin acts directly on the cells of the liver and skeletal muscles where it stimulates oxidation of fatty acids in the mitochondria and therefore reduces the storage of fat in those tissues (but not in adipose tissues). Clearly, leptin plays a tremendous role in regulating human body fat levels and the impact of exercise and diet on those stores.
The Role of THC in the regulation of Appetite
New research suggests that endocannabinoids are part of the brain's complex system for controlling when and how much to eat. It is known for some time that leptin is the key hormone for the regulation of the circuit in the hypothalamus responsible for appetite control. Leptin reduces food intake by upregulating appetite-reducing factors and downregulating appetite-stimulating factors. The finding that endocannabinoids (anandamide and 2-arachidonyl glycerol) are involved in this process helps explain why people get hungry after using cannabis or THC and why it helps patients with loss of appetite and weight.
In the study published in the journal Nature, researchers found that mice without CB1 cannabinoid receptors ate less than normal mice did. And when ordinary mice were given the cannabinoid receptor antagonist SR141716A that blocked endocannabinoids from acting at these receptors, they ate less than normal as well. Furthermore, reduced levels of leptin were associated with elevated levels of endocannabinoids in the hypothalamus, and application of leptin reduced endocannabinoid levels. These findings indicate that endocannabinoids in the hypothalamus may activate CB1 receptors to maintain food intake, and that they can act independently of the level of certain other appetite-triggering substances [23].
Recent research by Dr Rachel Wilson, University of California at San Francisco, discovered that the main ingredient in cannabis - delta 9- trans-tetrahydrocannabinol- or THC- is very similar in shape to endocannabinoids (naturally occurring cannabinoids in the body), which are involved in many body and brain functions. Cannabinoid receptors are found liberally throughout the body and brain. This is why marijuana smokers report a diverse collection of sensations. Endocannabinoids play an important role in the hippocampus, a part of the brain involved in learning and memory. It is thought that these molecules help lay down new memories by strengthening connections between nerve cells. However, when the brain is flooded with cannabinoids through marijuana use, forgetfulness results. They also appear to tone down the production of certain neurotransmitters, acting like the brakes of a car when the system is racing too fast. Marijuana has also been implicated in the dopaminergic system and it is thought that through a complex chain of events, revs up the dopamine system. One study showed a complex interplay existed between cannabinoids and leptin, a hormone that produces satiety and is probably the reason why marijuana users get the "munchies" [24].
It appears clear that THC boosts appetite and appears to have an inverse relationship with leptin levels in the brain. For an athlete or bodybuilding seeking to get down to a certain level of body fat for a competition, ingesting THC would appear to be counter-indicated. Not only does THC drastically increase appetite, but also it may hinder fat burning in the body and negatively effect metabolic processes that are already impaired in a low-calorie environment. However, for athletes who have a difficult time increasing their weight, such as an off-season bodybuilder, THC may be useful if only for very limited periods of time.
Concluding Remarks
Drug hysteria has long been a part of our culture – consider the classic film Reefer Madness. Images of drug-depraved madmen doing anything to feed their habit have been captures in all contemporary forms of media. But, as far as marijuana and THC are concerned, there appears to be very little cause for alarm. For the bodybuilder or athlete, THC has some interesting and maybe even attractive applications; lowering blood pressure, suppressing muscle pain and soreness without resorting to physically addictive opiates, and for some, stimulating appetite. THC would seem to be a much better choice for these benefits then the opiate derived drugs like nalbuphine (Nubain). However, THC remains illegal and that in itself carries certain risks to use. If anyone chooses to use narcotics or to self-medicate, they are taking their health into their own hands so at the very least, they can educate themselves of the risks and benefits. That is the hope of this THC Unbound article, to educate and inform without advancing a particular ideal
i cut some parts out, to make it a bit easier to read
THC Unbound
by Grendel
THC Pharmacology
THC, as found in marijuana is usually smoked but can be eaten. THC can also be injected intravenously. Peak plasma levels are reached ten minutes after smoking. The psychoactive components are effective for two to three hours, however THC has a long half-life due to its lipid soluble nature and redistribution into fatty tissue. THC can be detected in urine months after initial administration. THC is metabolized through the cytochrome P450 system. Approximately one third is eliminated renally and two-thirds through fecal excretion. The LD-50 (lethal dose for 50 percent of those administered that amount of the drug) is 1270mg/kg in male rats and 730mg/kg in female rats (when taken orally in sesame oil). The LD-50 from inhalation is 42mg/kg in rats [6]. Generally speaking, it would be almost impossible for a human to overdose on THC.
THC and Sex Hormones
For the athlete and bodybuilder, hormones are extremely important. Testosterone, the male sex hormone, is responsible for muscle growth, strength, and body composition. Synthetic testosterone, and its derivate anabolic steroid relatives, are used to enhance athletic performance and used, aesthetically, by bodybuilders to develop larger stronger muscles. Even for athletes who do not use performance enhancing anabolic hormones, it is extremely important to keep natural product of sex hormones at the right levels if not slightly elevated through proper diet, training, and nutrition. Therefore, any serious athlete should investigate the impact of any chemical on their endogenous hormone product.
The traditional standpoint is that THC negatively impacts the hormonal profile of users, specifically decreases the amount of testosterone produced by the body, increasing estrogen levels in men, and reducing sperm motility (fertility). These findings are typically based on tests on animals, extrapolated to apply to humans. However, the scientific findings are hardly conclusive and, in fact, seem to dispute the hypothesis that THC has any negative impact on human hormone levels.
A study by at the University of Iowa, in 1991, disputed that common belief that THC affected the levels of testosterone and other sex hormones in the human body. The study was a direct contradiction of the 1974 study, by Dr. R.C. Kolodny, which reported a decrease in testosterone levels in men who smoked marijuana regularly and helped found the common belief that THC was responsible for feminizing effects on men. The University of Iowa study found that chronic marijuana use had no effect on testosterone, luteinizing hormone, and follicle stimulating hormone, prolactin and cortisol in men or women. The study also noted that six other studies has failed to show lower testosterone, leading the Iowa study to conclude that “it appears that marijuana, even heavy use of the kind that is typical in the United States, doesn’t alter testosterone levels.” However, the study did caution that heavy prolonged use might have other adverse effects, including “possible effects on reproductive function and mild, selective cognitive impairments associated with heavy, chronic use.” [18]
A 1994 study found that THC probably does disrupt the male and female reproductive system and hormones, at least in animals. The study found a reduction in the secretion of testosterone and therefore reduced sperm production, viability, and motility in human males; this means that male fertility was negatively impacted. The study did admit that it was unclear whether this data could be applied to humans and recognized that cannabinoids have both negative and positive effects on testosterone levels in humans. One of the study’s authors postulated that the impact of THC on grown human males would be minimal, but that the impact would be more profound on pre-pubescent males. [19]
A 1997 study showed that THC, administered in large dosages on animals, does seem to affect sex hormone levels. However the effects vary from one study to the next and when effects do occur, they are temporary and highly dependent on dosage and timing of the THC administration. The study concluded that it was possible that THC might cause infertility in men with already low sperm counts, but that it was unlikely to effect healthy subjects. Additionally, the study stated that users develop a tolerance to any hormonal effects of THC. The study concluded that THC has neither a feminizing effect in males nor a masculinizing effect in females [20].
But a 1998 study showed that cannabinoids, in animals, caused alterations in both male and female sexual hormones but there was no evidence that THC adversely effected human fertility of caused any chromosomal or genetic damage as some critics postulated that THC would do [21].A 2001 study concluded that cannabis smoking decreased the blood levels of three hormones; luteinizing hormone (LH), follicle stimulating hormone (FSH), and testosterone. The study also found a lower sperm count in men who were reported heavy marijuana smokers. But other studies did not measurable differences in men who were light or heavy users of THC. Acute THC treatment did produce a consistent and significant dose- and time-related decrease in LH and testosterone in male rodents; and in male rhesus monkeys an acute dose of THC produced a 65% reducing in blood testosterone levels within 60 minutes of treatment and lasting for approximately 24 hours [22].
The general conclusion seems to be that even heavy use of THC in all its forms has little impact on health human hormone levels. If there are any effects, they appear to be short lived and dosage dependent. It seems unlikely that an advanced athlete would be harmed by occasional use of THC for other purposes, particularly the stimulation of appetite.
THC and Leptin: The Weight loss and Appetite Link
A brief overview of Leptin
There are several breeds of laboratory mice that have a single-gene mutation that causes them to become extremely fat, clinically obese. These mice fall into two classes; mice with the genotype ob/ob which involves a mutation in the gene for the protein hormone leptin and db/db which involve mutations in the gene that encoded the receptor for the hormone leptin. When ob/ob mice are treated with injections of leptin they lose their fat and return to a healthy normal body weight.
Leptin is manufactured in fat cells or adipose tissue and circulating levels of leptin are directly linked to overall fat content of the body. Leptin acts on receptors in the hypothalamus of the brain where leptin:
• Counteracts the effects of neuropeptide Y (a potent feeding stimulant secreted by cells in the gut and in the hypothalamus);
• Counteracts the effects of anadamide (another potent feeding stimulant that binds to the same receptors as THC, the active ingredient of marijuana)
• Promotes the effects of alpha-MSH, an appetite suppressant;
The result is the inhibition of food intake. Thus leptin provides homeostatic control of food intake. It is the absence of a function hormone or its corresponding receptor that leads to uncontrolled food intake and resulting obesity. In addition to effecting the hypothalamus, leptin acts directly on the cells of the liver and skeletal muscles where it stimulates oxidation of fatty acids in the mitochondria and therefore reduces the storage of fat in those tissues (but not in adipose tissues). Clearly, leptin plays a tremendous role in regulating human body fat levels and the impact of exercise and diet on those stores.
The Role of THC in the regulation of Appetite
New research suggests that endocannabinoids are part of the brain's complex system for controlling when and how much to eat. It is known for some time that leptin is the key hormone for the regulation of the circuit in the hypothalamus responsible for appetite control. Leptin reduces food intake by upregulating appetite-reducing factors and downregulating appetite-stimulating factors. The finding that endocannabinoids (anandamide and 2-arachidonyl glycerol) are involved in this process helps explain why people get hungry after using cannabis or THC and why it helps patients with loss of appetite and weight.
In the study published in the journal Nature, researchers found that mice without CB1 cannabinoid receptors ate less than normal mice did. And when ordinary mice were given the cannabinoid receptor antagonist SR141716A that blocked endocannabinoids from acting at these receptors, they ate less than normal as well. Furthermore, reduced levels of leptin were associated with elevated levels of endocannabinoids in the hypothalamus, and application of leptin reduced endocannabinoid levels. These findings indicate that endocannabinoids in the hypothalamus may activate CB1 receptors to maintain food intake, and that they can act independently of the level of certain other appetite-triggering substances [23].
Recent research by Dr Rachel Wilson, University of California at San Francisco, discovered that the main ingredient in cannabis - delta 9- trans-tetrahydrocannabinol- or THC- is very similar in shape to endocannabinoids (naturally occurring cannabinoids in the body), which are involved in many body and brain functions. Cannabinoid receptors are found liberally throughout the body and brain. This is why marijuana smokers report a diverse collection of sensations. Endocannabinoids play an important role in the hippocampus, a part of the brain involved in learning and memory. It is thought that these molecules help lay down new memories by strengthening connections between nerve cells. However, when the brain is flooded with cannabinoids through marijuana use, forgetfulness results. They also appear to tone down the production of certain neurotransmitters, acting like the brakes of a car when the system is racing too fast. Marijuana has also been implicated in the dopaminergic system and it is thought that through a complex chain of events, revs up the dopamine system. One study showed a complex interplay existed between cannabinoids and leptin, a hormone that produces satiety and is probably the reason why marijuana users get the "munchies" [24].
It appears clear that THC boosts appetite and appears to have an inverse relationship with leptin levels in the brain. For an athlete or bodybuilding seeking to get down to a certain level of body fat for a competition, ingesting THC would appear to be counter-indicated. Not only does THC drastically increase appetite, but also it may hinder fat burning in the body and negatively effect metabolic processes that are already impaired in a low-calorie environment. However, for athletes who have a difficult time increasing their weight, such as an off-season bodybuilder, THC may be useful if only for very limited periods of time.
Concluding Remarks
Drug hysteria has long been a part of our culture – consider the classic film Reefer Madness. Images of drug-depraved madmen doing anything to feed their habit have been captures in all contemporary forms of media. But, as far as marijuana and THC are concerned, there appears to be very little cause for alarm. For the bodybuilder or athlete, THC has some interesting and maybe even attractive applications; lowering blood pressure, suppressing muscle pain and soreness without resorting to physically addictive opiates, and for some, stimulating appetite. THC would seem to be a much better choice for these benefits then the opiate derived drugs like nalbuphine (Nubain). However, THC remains illegal and that in itself carries certain risks to use. If anyone chooses to use narcotics or to self-medicate, they are taking their health into their own hands so at the very least, they can educate themselves of the risks and benefits. That is the hope of this THC Unbound article, to educate and inform without advancing a particular ideal
