High-Dose Glycine For OCD And BDD

[Jib]

High-Dose Glycine Treatment of Refractory Obsessive-Compulsive Disorder and Body Dysmorphic Disorder in a 5-Year Period

High-Dose Glycine Treatment of Refractory Obsessive-Compulsive Disorder and Body Dysmorphic Disorder in a 5-Year Period

Treatment with glycine, an NMDAR coagonist, over 5 years led to robust reduction of OCD/BDD signs and symptoms except for partial relapses during treatment cessation. Education and social life were resumed and evidence suggests improved cognition. Our findings motivate further study of glycine treatment of OCD and BDD.

Target doses varied from 50 to 66 g/day (0.6–0.8 grams of glycine per kilogram of body weight).

 

[erho]

I’ve been meaning to give this a shot. I am worried about the potential side effects though. I will probably start very slow and increase every other day. Last time I took pure glycine I got some bad headaches.

 

[Jib]

I’ve been meaning to give this a shot. I am worried about the potential side effects though. I will probably start very slow and increase every other day. Last time I took pure glycine I got some bad headaches.

I wonder why? The dose in this study seems exceptionally high. I'm currently doing about 8g - 10g a day and am still unsure if it's related to IBS-like symptoms I've been having, mostly diarrhea/loose stools. I've had days where I supplemented glycine and did not have these issues so it makes me think it's something else.

Were you taking it on an empty stomach or with food? How much were you taking, and was it all at once or in divided doses? I wonder if that makes any difference.

Platelet glycine, glutamate and aspartate in primary headache. - PubMed - NCBI

I'd like to think glycine is very safe to take even in higher amounts, but it's possible there are contraindications. In my experience over the past few weeks taking glycine, it seems to have helped with improving my mood a bit. Less stressed out, less attachment to things that were previously bothering me a lot. I still have the same issues and they still bother me, but there's noticeably less attachment/obsession/ruminating. Still some, but not as much. FWIW I'm generally mixing glycine with a couple grams each of taurine and creatine as well.

Haven't tried higher doses yet. Again, the amount here is exceptionally high, and I'm hesitant myself to try such amounts (50g - 60g daily).

 

[erho]

I would only do it for mental health, pretty much. But I would try to get up to around 15 grams twice a day.

I think the reason I got headaches in the past could be that I didnt consume enough magnesium and a low blood sugar reaction. Even though I did take it with food, I think my glucose metabolism at the time wasnt optimal.

 

[shine]

I would only do it for mental health, pretty much. But I would try to get up to around 15 grams twice a day.

I think the reason I got headaches in the past could be that I didnt consume enough magnesium and a low blood sugar reaction. Even though I did take it with food, I think my glucose metabolism at the time wasnt optimal.

Glycine in low doses dilates the microvessels in the brain 200%+. Maybe that has something to do with it.

 

[cjm]

I'd like to think glycine is very safe to take even in higher amounts, but it's possible there are contraindications. In my experience over the past few weeks taking glycine, it seems to have helped with improving my mood a bit. Less stressed out, less attachment to things that were previously bothering me a lot. I still have the same issues and they still bother me, but there's noticeably less attachment/obsession/ruminating. Still some, but not as much. FWIW I'm generally mixing glycine with a couple grams each of taurine and creatine as well.

Hey Jib! Nice post.

Glycine is dose dependent, I can vouch for that. More is needed to achieve therapeutic concentrations in the brain relative to the plasma. I had to take 30g to get the GABA-like effect (I also have GABA on hand to experiment with). Haidut calculated that "oral glycine doses in the range of 500mg - 16g are needed to achieve the effective concentration in the brain."

Glycine/GABA and derivatives can be used as performance enhancers. I was reading about GHB in bodybuilding and it was claimed to increase growth hormone and muscle mass but it induced deep sleep (@mrchibbs) like no other. That's why it is so addictive.

Glycine is helping me get "grounded" per the body psychotherapy tradition of Reich and Lowen. Grounding discharges excessive charge in the body. Glycine is anti-excitatory.

 

[cjm]

Dug in a little. Dude makes big progress when he's taking high doses for a while:

Observation Period 5 - "[SAT] verbal score was in the 90th percentile and was 60 points higher than the best practice test and 120 points higher than the first practice test"
Observation Period 9 - "first date with a girlfriend in 13 years"

Falls off a cliff after OP9, it was the longest he had abstained after initiating treatment.

They stopped treatment 5 times. Except for the first time when he had a fever during an infection, the reason given was weight loss.

Glycine was not thought to cause the fever or the weight loss.

HOWEVER

There is mention of elevated blood ammonia after injection of 20g. They didn't think it was an issue for the subject.

"As noted previously, high-dose glycine treatment may lead in some individuals to mildly elevated plasma ammonia. This could lead to elevated levels of ammonia in the brain. Studies in rats have indicated that moderate levels of chronic hyperammonemia inhibit NMDAR neurotransmission [127]. This raises the possibility that optimal glycine therapy in individuals with elevated ammonia would require a coadministered agent to control ammonia."

3.5.12. Adverse Effects of High-Dose Glycine?​

Ingested glycine appears to enter circulation rapidly, generating a sharp rise in plasma glycine concentration. In O's case, multiple measurements at approximately two hours after completion of consumption have yielded values ranging from ~2600 to ~3300 μM, with an average of ~2800. The time at which peak concentration is reached is unknown, but may be less than 2 hours after ingestion and may depend on the rate at which glycine is consumed and on the presence of other food in the stomach. On one occasion, a plasma value obtained at 3 hours after glycine ingestion (~1350 μM) was substantially less than values obtained at 2 hours (~2000–3000 μM) (normal reference 151–490 μM). On another occasion, 24 hours after terminating an extended period of glycine consumption, plasma glycine was ~280 μM, a base-line value in the reference range (151–490 μM). This observation is consistent with studies of healthy volunteers by Hahn and Sandfeldt, who found the half-life of excess plasma glycine to range from 40 to 100 minutes in many individuals to 6 hours in one individual [53].

Hahn and Sandfeldt also found that glycine infusion in amounts comparable to those used in this study induced little or no increase of plasma ammonia in most individuals [54]. However, about 10–15% of healthy volunteers developed plasma ammonia levels in the 100 μM range after i.v. infusion of 20 g of glycine [54]. O appears to be in this category. For example, in a typical measurement, plasma ammonia about 2 hours after glycine ingestion was ~120 μM (reference: ≤47 μM). Orotic acid in urine at this time was ~15 mmol/mol/creatinine (reference: 0.4–1.2). Several physicians, including specialists on hepatic encephalopathy and urea cycle disorders, have suggested that the mild hyperammonemia seen in O is unlikely to cause harm. Nonetheless, hyperammonemia represents an issue that, to our knowledge, has not been studied in prior trials.

As noted previously, OP1 was terminated because of a fever of 104.2°F during an upper respiratory infection. At that time, O and his parents could not recall a fever this high in previous infections and worried that glycine might cause elevated temperatures. However, no high fevers have been experienced in the subsequent four years, during which glycine was taken for 850 days. In this period, the only precaution has been to terminate glycine at the first sign of an infection. Although there is no clear evidence for glycine inducing higher-than-normal fevers, we include these findings for future reference, since there is literature suggesting a role of NMDAR-ST in the fever response to bacterial toxins [55].

Mild weight loss with no obvious cause led to the termination of OP9. On the basis of sporadic measurements, weight declined from 184 pounds to 165 pounds over a period of 22 weeks. Glycine consumption was completely stopped and weight remained at this level for 17 weeks. Weight then increased to 172 pounds over a period of 8 weeks. Over the next 6 months, weight gradually returned to prior levels with no deliberate effort to increase weight. As noted in the section for OP10, there were no signs of anorexia nervosa or other eating disorders. At this point there is no clear evidence for glycine as the cause of weight loss.

In summary, available evidence suggests that high-dose glycine treatment used for a total of 947 days in a five-year observation period has not produced any detectable, serious adverse affects in an individual closely monitored by his physicians. This observation is in agreement with the apparent absence of serious adverse effects in the 20 years of glycine trials with schizophrenia [56].

 

[cjm]

Study:

"Raynaud's disease was first noticed at age 21 just after the end of a taper of paroxetine from 70 mg/day to 0 mg/day. It has been witnessed on several occasions in clinical exams and continues to the present day."

Wiki:

"Based on evidence from four weeks of administration in rats, the equivalent of 20 mg paroxetine taken once daily occupies approximately 88% of serotonin transporters in the prefrontal cortex."

 

[cjm]

I did a little experiment with 30g glycine in 2 divided doses over the last two days. My Phase I trial for safety. 15g is too much in one sitting: I threw up the last dose taken yesterday after a small bite of a sandwich, it was painful, I started sweating profusely but then felt pressure relief in my chest. Not much changed with my mental state. Still tunnel-y, foggy, distracted.

I suspect ammonia is an issue. I found this forum back in 2012 after a bout of exhaustive exercise that would take weeks to recover from. At some point, my "lows" turned into the new normal. I still can't move around a lot without my heart racing and lactic acid build-up. Ammonia smell still pours out of my armpits. Exercise fatigue is associated with hyperammonemia: Exercise-induced hyperammonemia: peripheral and central effects

Per the OP study's suggestion, I co-administered an anti-ammonia agent (sodium benzoate, 1g) this morning and feel the fog clearing. No glycine back in yet. I'm seeing if taurine can fill in.

 

[Digital Samurai]

I did a little experiment with 30g glycine in 2 divided doses over the last two days. My Phase I trial for safety. 15g is too much in one sitting: I threw up the last dose taken yesterday after a small bite of a sandwich, it was painful, I started sweating profusely but then felt pressure relief in my chest. Not much changed with my mental state. Still tunnel-y, foggy, distracted.

I suspect ammonia is an issue. I found this forum back in 2012 after a bout of exhaustive exercise that would take weeks to recover from. At some point, my "lows" turned into the new normal. I still can't move around a lot without my heart racing and lactic acid build-up. Ammonia smell still pours out of my armpits. Exercise fatigue is associated with hyperammonemia: Exercise-induced hyperammonemia: peripheral and central effects

Per the OP study's suggestion, I co-administered an anti-ammonia agent (sodium benzoate, 1g) this morning and feel the fog clearing. No glycine back in yet. I'm seeing if taurine can fill in.

Any update? How you going?

(i've been also experimenting with larger doses of glycine and have been having better results so far)