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GHB is Gamma hydroxybutyrate. GHB has been around for years, but in 1999, it took Rohypnol’s place when it became known as the date rape drug. Bodybuilders have long been interested in GHB for promoting restorative sleep and for its possible growth hormone (GH) release connection. In the last year a great deal of new research has been done on GHB that indicates that at controlled dosages, its side effects are practically non-existent and that there is a definitely a connection between GHB and GH release.
In this issue of Elite Fitness News, we’ll look at the new research on GHB. We’ll also look at how bodybuilders are using it to aid in muscle development and improve recovery times. We’ll also take a look at some of the latest research that indicates that many of the side effects attributed to GHB by the media were largely unfounded.
In May of 1999, our friends at the FDA recommended that GHB become a Schedule I Controlled Substance. In September of that year, the House of Representatives voted 423 to 1, and the Senate voted unanimously in favor of the FDA’s recommendations. And by November, the Drug Enforcement Agency was treating GHB just like heroin and other Schedule I drugs. In early 2000, President Clinton signed the legislation.
However, an important exception was made in the legislation. President Clinton said in a White House statement: “The Act will not impede ongoing research into the potential legitimate use of this drug to treat the special needs of those suffering from narcolepsy. Indeed, this Act creates a special exemption that provides that the manufacture and distribution of this drug for properly approved research purposes will be subject to the physical security requirements of Schedule III rather than Schedule I.”
Although GHB is very easily and cheaply manufactured, for better or worse, the FDA gave the drug companies permission to study GHB for possible sale as a pharmaceutical. In essence, what had happened is that GHB went from being an inexpensive and effective sleep aid that had been available as an OTC or as a gray market supplement and re-regulated it for the benefit of the drug companies.
Around this time, Orphan Medical, a drug company in Minneapolis, began research into using GHB for the treatment of narcolepsy. They developed a medically formulated GHB product and given it the brand name Xyrem. Although certainly motivated by profit, Orphan Medical has conducted several studies that indicate that GHB or Xyrem should not be a demonized Schedule I drug. Their research further indicates that GHB is relatively safe and can be an effective treatment for sleep disorders.
All of Orphan’s studies have involved the use of GHB to treat narcoleptics. Narcolepsy is a chronic neurological disorder affecting an estimated 100,000 to 125,000 Americans. The main symptoms are excessive daytime sleepiness and cataplexy. Cataplexy is a debilitating symptom characterized by loss of muscle control in response to strong emotions such as laughter, anger, or surprise. In its most severe form, cataplexy can cause a person to collapse during waking hours.
Of primary interest to us as bodybuilders is how a narcoleptic’s sleep patterns differ from the sleep patterns of a normal person. When you and I sleep, our sleep is divided into 5 stages. Stages 1 through 4 are the non-REM stages. Stage 5 is the REM stage. REM stands for Rapid Eye Movement. REM sleep is distinguishable from Non-REM sleep by changes in physiological states, where heart rate increases, respiration speeds up and becomes erratic, and the face, fingers, and legs may twitch. Intense dreaming occurs during REM sleep as a result of heightened cerebral activity, but paralysis occurs simultaneously in the major voluntary muscle groups. Here’s what happens in a healthy sleep cycle.
The Non-REM Stages
Stage 1
Stage 1 sleep is essentially drowsiness. Polysomnography shows a 50% reduction in activity between wakefulness and stage 1 sleep. The eyes are closed during stage 1 sleep, but if aroused from it, you feel like you have not slept. Stage 1 lasts for about 10 minutes.
Stage 2
Stage 2 is a period of light sleep during which polysomnographic readings show intermittent peaks and valleys, or positive and negative waves. These waves indicate spontaneous periods of muscle tone mixed with periods of muscle relaxation. The heart rate slows, and body temperature decreases. At this point, the body prepares to enter deep sleep.
Stages 3 and 4
These are deep sleep stages and the ones we are primarily concerned with as bodybuilders. Stage 4 is more intense than stage 3. These stages are known as slow-wave, or delta-sleep. During slow-wave sleep, especially during stage 4, the electromyogram records slow waves of high amplitude, indicating a pattern of deep sleep.
Studies have tracked the levels of certain hormones during the sleep cycle -- in particular, the release of growth hormone (GH). In men, but not in women, 60 to 70 percent of the body's GH is secreted during the slow-wave stage of sleep. Interestingly, studies have shown that, infants and adolescents have higher levels of GH and also spend much more time in stages 3 and 4 sleep. Obviously, both infants and adolescents are in a state of rapid growth. Other research has shown that as men move from early adulthood (16 to 25 years) into middle age (36 to 50 years), the time spent in slow wave sleep decreases by about 15 percent. This corresponds to a drop in GH production and possibly to what we commonly call "middle-aged spread."
Non-REM Sleep
The period of non-REM sleep is comprised of stages 1-4 and lasts from 90 to 120 minutes, each stage lasting anywhere from 5 to 15 minutes. Surprisingly, however, Stages 2 and 3 repeat backwards before REM sleep is attained. So, a normal sleep cycle has this pattern: waking, stage 1, 2, 3, 4, 3, 2, REM. Usually, REM sleep occurs 90 minutes after sleep onset.
After analyzing their findings, the researchers suggested that it might be possible to "treat" the aging process in men by adjusting their sleep patterns. Also, medications that enhance the slow wave phase of sleep could possibly help compensate for medically low GH levels in younger people. More research is needed to determine if this is a practical solution. However the study supports the idea that sleep patterns can be related to metabolism as well.
The five stages of sleep, including their repetition, occur cyclically. The first cycle, which ends after the completion of the first REM stage, usually lasts for 100 minutes. Each subsequent cycle lasts longer, as its respective REM stage extends. So a person may complete five cycles in a typical night’s sleep.
A narcolepsy patient typically enters into REM sleep soon after falling asleep. This abnormal phenomenon is part of the diagnostic profile of narcolepsy. As such, the narcoleptic is largely deprived of the benefits of stage 3 and 4 sleep and the associated GH release. So, Orphan Medical began several studies where GHB or Xyrem, as they call it, was administered to narcoleptics. The results were very promising both for narcolepsy patients, aging men, and for bodybuilders.
The data from the trials demonstrated an overall improvement in both the quality and integration of sleep for narcolepsy patients being treated with Xyrem, as well as a reduction in daytime sleepiness. The trial was conducted over 14 weeks with 21 individuals with narcolepsy. Xyrem produced a dose-related increase in slow-wave (stage 3-4) sleep, with a corresponding reduction in stage 1 sleep. Slow wave sleep is the restorative stage of sleep. These changes in the restorative components of sleep were accompanied by a decrease in the number of nocturnal awakenings, reaching statistical significance at the 7.5 and 9-gram doses.
After the first night of dosing, a significant increase in REM sleep was measured in all-night recordings. Over the course of the trial as the time spent in stage 3 and 4 sleep increased, the total time spent in the Rapid Eye Movement (REM) stages of sleep decreased. These changes were accompanied by a decreasing trend in the shifts between sleep stages, although the total sleep time did not change.
The first Orphan Medical trial evaluated three dosage levels of Xyrem in a four-week, placebo-controlled, double-blind study. The study involved 136-patients, and was conducted at 18 sleep centers around the country. Medications intended to control cataplexy were discontinued over three to four weeks upon each patient’s entry into the trial. This action was followed by a “washout” period of 5 to 18 days during which the effects of any such medication were eliminated. Each patient’s untreated symptoms were recorded in daily diaries over a baseline period of 14 to 21 days. After this baseline period, patients were randomly assigned a placebo or an active dose level of 3, 6, or 9 grams of Xyrem. All cataplexy events were recorded daily over four weeks.
After the first trial, all patients, including those previously taking the placebo, were given the opportunity to enter into a follow-up study. After another short washout period, the 118 patients in this second trial were provided active the drug, titrated to levels deemed clinically effective by physician investigators.
During the first trial, the number of weekly cataplexy attacks in patients who received the 9-gram dose of Xyrem decreased by 68.6% in comparison to the baseline. When compared to the placebo response, the clinical improvement of patients on the 9-gram Xyrem dose was highly statistically significant, with ever less improvement noted with the 6 and 3 gram doses.
At the end of the four-week trial, it appeared that the treatment response in patients taking the 6 and 9 gram doses had not reached a plateau. This was confirmed in the follow-on trial that measured each patient’s response to Xyrem across the following 30 weeks. Data from the second trial suggest that maximum benefit was reached in seven weeks for most patients and was then sustained.
What about side effects?
As you know, the media has demonized GHB and claimed that it has a horrific side effect profile. Specifically, they have suggested that GHB has been the cause of respiratory failure in some users.
In the Xyrem trials, respiratory data was collected and analyzed to determine if the escalating doses of Xyrem (4.5 to 9g/night) would cause sleep-disordered breathing or reduced oxygenation during sleep. The results were very positive. No respiratory depressant effects were identified from therapeutic doses of Xyrem.
The results showed no dose-related changes in mean saturated oxygen values in arterial blood (SaO2), with mean values maintained between 94.7% and 95.5%. Since previous studies indicated that peak plasma concentrations occurred 30-60 minutes after dosing, and that higher plasma levels occurred in relation to the second nightly dose compared to the first, special attention was paid to these times of expected peak plasma concentrations. No changes in arterial oxygen saturation corresponded to these times.
Minor, variable changes in the incidence and severity of events of sleep - disordered breathing occurred throughout the study. These were classified largely as sleep apneas. However, dose-related changes were not seen in the therapeutic dose range of 4.5 to 9g/night in incidence of events.
Although generally well tolerated, there were some observed side effects from Xyrem. Most side effects appeared to be dose related and often occurred early during the trials and abated over time. The most common adverse events were dizziness, nausea, headache, and enuresis (urinary incontinence during sleep).
In conclusion, I think it is clear that GHB definitely does increase the GH releasing stage 3 and stage 4 sleep levels as indicated by the research on narcoleptics. Stage 3 and stage 4 sleep levels are also the most restorative sleep levels and there are definite benefits to their prolongation. It is important to note that Xyrem is a pharmaceutical grade GHB – not the bathtub variety found on the streets. Additionally, the dosing conditions were largely pristine, meaning that there was no interplay with other substances in the subjects studied.
As I mentioned a few weeks ago in my article on Modafinil, relatively little is known about sleep compared to say what we know about nutrition. Modafinil, as you may remember is also used to treat narcolepsy. Modafinil is as effective as amphetamine in promoting wakefulness, but has none of the side effects. It would be interesting to see studies, which will certainly be forthcoming, that look at patients treated with Modafinil during the day and Xyrem at night. It would stand to reason, that soon we may be able to use these two compounds to reduce our need for sleep to say only 24 hours per week, while at the same time, increase the quality and benefits obtained from the time we are spending asleep.
If any of you have tried a Modafinil/GHB combination, or have comments on GHB itself, I would appreciate your posting them.
GHB is Gamma hydroxybutyrate. GHB has been around for years, but in 1999, it took Rohypnol’s place when it became known as the date rape drug. Bodybuilders have long been interested in GHB for promoting restorative sleep and for its possible growth hormone (GH) release connection. In the last year a great deal of new research has been done on GHB that indicates that at controlled dosages, its side effects are practically non-existent and that there is a definitely a connection between GHB and GH release.
In this issue of Elite Fitness News, we’ll look at the new research on GHB. We’ll also look at how bodybuilders are using it to aid in muscle development and improve recovery times. We’ll also take a look at some of the latest research that indicates that many of the side effects attributed to GHB by the media were largely unfounded.
In May of 1999, our friends at the FDA recommended that GHB become a Schedule I Controlled Substance. In September of that year, the House of Representatives voted 423 to 1, and the Senate voted unanimously in favor of the FDA’s recommendations. And by November, the Drug Enforcement Agency was treating GHB just like heroin and other Schedule I drugs. In early 2000, President Clinton signed the legislation.
However, an important exception was made in the legislation. President Clinton said in a White House statement: “The Act will not impede ongoing research into the potential legitimate use of this drug to treat the special needs of those suffering from narcolepsy. Indeed, this Act creates a special exemption that provides that the manufacture and distribution of this drug for properly approved research purposes will be subject to the physical security requirements of Schedule III rather than Schedule I.”
Although GHB is very easily and cheaply manufactured, for better or worse, the FDA gave the drug companies permission to study GHB for possible sale as a pharmaceutical. In essence, what had happened is that GHB went from being an inexpensive and effective sleep aid that had been available as an OTC or as a gray market supplement and re-regulated it for the benefit of the drug companies.
Around this time, Orphan Medical, a drug company in Minneapolis, began research into using GHB for the treatment of narcolepsy. They developed a medically formulated GHB product and given it the brand name Xyrem. Although certainly motivated by profit, Orphan Medical has conducted several studies that indicate that GHB or Xyrem should not be a demonized Schedule I drug. Their research further indicates that GHB is relatively safe and can be an effective treatment for sleep disorders.
All of Orphan’s studies have involved the use of GHB to treat narcoleptics. Narcolepsy is a chronic neurological disorder affecting an estimated 100,000 to 125,000 Americans. The main symptoms are excessive daytime sleepiness and cataplexy. Cataplexy is a debilitating symptom characterized by loss of muscle control in response to strong emotions such as laughter, anger, or surprise. In its most severe form, cataplexy can cause a person to collapse during waking hours.
Of primary interest to us as bodybuilders is how a narcoleptic’s sleep patterns differ from the sleep patterns of a normal person. When you and I sleep, our sleep is divided into 5 stages. Stages 1 through 4 are the non-REM stages. Stage 5 is the REM stage. REM stands for Rapid Eye Movement. REM sleep is distinguishable from Non-REM sleep by changes in physiological states, where heart rate increases, respiration speeds up and becomes erratic, and the face, fingers, and legs may twitch. Intense dreaming occurs during REM sleep as a result of heightened cerebral activity, but paralysis occurs simultaneously in the major voluntary muscle groups. Here’s what happens in a healthy sleep cycle.
The Non-REM Stages
Stage 1
Stage 1 sleep is essentially drowsiness. Polysomnography shows a 50% reduction in activity between wakefulness and stage 1 sleep. The eyes are closed during stage 1 sleep, but if aroused from it, you feel like you have not slept. Stage 1 lasts for about 10 minutes.
Stage 2
Stage 2 is a period of light sleep during which polysomnographic readings show intermittent peaks and valleys, or positive and negative waves. These waves indicate spontaneous periods of muscle tone mixed with periods of muscle relaxation. The heart rate slows, and body temperature decreases. At this point, the body prepares to enter deep sleep.
Stages 3 and 4
These are deep sleep stages and the ones we are primarily concerned with as bodybuilders. Stage 4 is more intense than stage 3. These stages are known as slow-wave, or delta-sleep. During slow-wave sleep, especially during stage 4, the electromyogram records slow waves of high amplitude, indicating a pattern of deep sleep.
Studies have tracked the levels of certain hormones during the sleep cycle -- in particular, the release of growth hormone (GH). In men, but not in women, 60 to 70 percent of the body's GH is secreted during the slow-wave stage of sleep. Interestingly, studies have shown that, infants and adolescents have higher levels of GH and also spend much more time in stages 3 and 4 sleep. Obviously, both infants and adolescents are in a state of rapid growth. Other research has shown that as men move from early adulthood (16 to 25 years) into middle age (36 to 50 years), the time spent in slow wave sleep decreases by about 15 percent. This corresponds to a drop in GH production and possibly to what we commonly call "middle-aged spread."
Non-REM Sleep
The period of non-REM sleep is comprised of stages 1-4 and lasts from 90 to 120 minutes, each stage lasting anywhere from 5 to 15 minutes. Surprisingly, however, Stages 2 and 3 repeat backwards before REM sleep is attained. So, a normal sleep cycle has this pattern: waking, stage 1, 2, 3, 4, 3, 2, REM. Usually, REM sleep occurs 90 minutes after sleep onset.
After analyzing their findings, the researchers suggested that it might be possible to "treat" the aging process in men by adjusting their sleep patterns. Also, medications that enhance the slow wave phase of sleep could possibly help compensate for medically low GH levels in younger people. More research is needed to determine if this is a practical solution. However the study supports the idea that sleep patterns can be related to metabolism as well.
The five stages of sleep, including their repetition, occur cyclically. The first cycle, which ends after the completion of the first REM stage, usually lasts for 100 minutes. Each subsequent cycle lasts longer, as its respective REM stage extends. So a person may complete five cycles in a typical night’s sleep.
A narcolepsy patient typically enters into REM sleep soon after falling asleep. This abnormal phenomenon is part of the diagnostic profile of narcolepsy. As such, the narcoleptic is largely deprived of the benefits of stage 3 and 4 sleep and the associated GH release. So, Orphan Medical began several studies where GHB or Xyrem, as they call it, was administered to narcoleptics. The results were very promising both for narcolepsy patients, aging men, and for bodybuilders.
The data from the trials demonstrated an overall improvement in both the quality and integration of sleep for narcolepsy patients being treated with Xyrem, as well as a reduction in daytime sleepiness. The trial was conducted over 14 weeks with 21 individuals with narcolepsy. Xyrem produced a dose-related increase in slow-wave (stage 3-4) sleep, with a corresponding reduction in stage 1 sleep. Slow wave sleep is the restorative stage of sleep. These changes in the restorative components of sleep were accompanied by a decrease in the number of nocturnal awakenings, reaching statistical significance at the 7.5 and 9-gram doses.
After the first night of dosing, a significant increase in REM sleep was measured in all-night recordings. Over the course of the trial as the time spent in stage 3 and 4 sleep increased, the total time spent in the Rapid Eye Movement (REM) stages of sleep decreased. These changes were accompanied by a decreasing trend in the shifts between sleep stages, although the total sleep time did not change.
The first Orphan Medical trial evaluated three dosage levels of Xyrem in a four-week, placebo-controlled, double-blind study. The study involved 136-patients, and was conducted at 18 sleep centers around the country. Medications intended to control cataplexy were discontinued over three to four weeks upon each patient’s entry into the trial. This action was followed by a “washout” period of 5 to 18 days during which the effects of any such medication were eliminated. Each patient’s untreated symptoms were recorded in daily diaries over a baseline period of 14 to 21 days. After this baseline period, patients were randomly assigned a placebo or an active dose level of 3, 6, or 9 grams of Xyrem. All cataplexy events were recorded daily over four weeks.
After the first trial, all patients, including those previously taking the placebo, were given the opportunity to enter into a follow-up study. After another short washout period, the 118 patients in this second trial were provided active the drug, titrated to levels deemed clinically effective by physician investigators.
During the first trial, the number of weekly cataplexy attacks in patients who received the 9-gram dose of Xyrem decreased by 68.6% in comparison to the baseline. When compared to the placebo response, the clinical improvement of patients on the 9-gram Xyrem dose was highly statistically significant, with ever less improvement noted with the 6 and 3 gram doses.
At the end of the four-week trial, it appeared that the treatment response in patients taking the 6 and 9 gram doses had not reached a plateau. This was confirmed in the follow-on trial that measured each patient’s response to Xyrem across the following 30 weeks. Data from the second trial suggest that maximum benefit was reached in seven weeks for most patients and was then sustained.
What about side effects?
As you know, the media has demonized GHB and claimed that it has a horrific side effect profile. Specifically, they have suggested that GHB has been the cause of respiratory failure in some users.
In the Xyrem trials, respiratory data was collected and analyzed to determine if the escalating doses of Xyrem (4.5 to 9g/night) would cause sleep-disordered breathing or reduced oxygenation during sleep. The results were very positive. No respiratory depressant effects were identified from therapeutic doses of Xyrem.
The results showed no dose-related changes in mean saturated oxygen values in arterial blood (SaO2), with mean values maintained between 94.7% and 95.5%. Since previous studies indicated that peak plasma concentrations occurred 30-60 minutes after dosing, and that higher plasma levels occurred in relation to the second nightly dose compared to the first, special attention was paid to these times of expected peak plasma concentrations. No changes in arterial oxygen saturation corresponded to these times.
Minor, variable changes in the incidence and severity of events of sleep - disordered breathing occurred throughout the study. These were classified largely as sleep apneas. However, dose-related changes were not seen in the therapeutic dose range of 4.5 to 9g/night in incidence of events.
Although generally well tolerated, there were some observed side effects from Xyrem. Most side effects appeared to be dose related and often occurred early during the trials and abated over time. The most common adverse events were dizziness, nausea, headache, and enuresis (urinary incontinence during sleep).
In conclusion, I think it is clear that GHB definitely does increase the GH releasing stage 3 and stage 4 sleep levels as indicated by the research on narcoleptics. Stage 3 and stage 4 sleep levels are also the most restorative sleep levels and there are definite benefits to their prolongation. It is important to note that Xyrem is a pharmaceutical grade GHB – not the bathtub variety found on the streets. Additionally, the dosing conditions were largely pristine, meaning that there was no interplay with other substances in the subjects studied.
As I mentioned a few weeks ago in my article on Modafinil, relatively little is known about sleep compared to say what we know about nutrition. Modafinil, as you may remember is also used to treat narcolepsy. Modafinil is as effective as amphetamine in promoting wakefulness, but has none of the side effects. It would be interesting to see studies, which will certainly be forthcoming, that look at patients treated with Modafinil during the day and Xyrem at night. It would stand to reason, that soon we may be able to use these two compounds to reduce our need for sleep to say only 24 hours per week, while at the same time, increase the quality and benefits obtained from the time we are spending asleep.
If any of you have tried a Modafinil/GHB combination, or have comments on GHB itself, I would appreciate your posting them.
