THC & CBD & ASHTON

The Ashton Manual is a guideline, with a few updates, and it’s primary value is that no one else has bothered to address the devilish intricacies of coming off benzodiazepines.

Cannabis has been found to have many medical uses, but of course it can also be misused.

I don't believe that Ashton is being deified here on BB — the guide is simply a starting point and/or reference manual.

Same goes for cannabis. Discussions here are mostly about utilizing beneficial forms of it for the purposes of healing. I haven’t seen anybody talking about abusing it, or wanting to get irresponsibly ripped on it.

Knowledgeable members here tend to steer others away from strains that may exacerbate benzo symptoms.

What’s the problem specifically? 

Hi kpin99,

Thanks for posting this informative link.

I don't use it either, after doing the research on it.    It's up to each individual to make that choice.

Aston does point out some issues with cannibis in this article.  Unfortunately,  the article is quite dated (2001), and the latest cutting edge research from Israeli researchers were not available in full, at the time of the writing of the paper.

It does not read as an endorsement.  I skimmed it very quickly. 

She lists several physiological negative collateral effects in the last section

She does allude to some of these issues here.  (The coupling to GABAARs has been discovered by the latest research.....)

Quote

appears that both anandamides and their receptors reside within neuronal lipid membranes and act as neuromodula- tors through intracellular G-proteins con- trolling cyclic adenosine monophosphate formation and Ca2+ and K+ ion transport. In this role the system may have important

Table 2 Preparations of cannabis  USA and UK)

interactions with other neurotransmitters, including g-aminobutyric acid, opioid systems and monoamines. In particular, THC has been shown to increase the release of dopamine from the nucleus accumbens and prefrontal cortex  Tanda et al, 1997). This effect, which is common to many drugs of misuse  including heroin, cocaine, amphetamine and nicotine), may be the basis of its reinforcing properties and its....

End quote

And this, i.e. Accumulation in fatty tissue

Quote

Because they are extremely lipid soluble, cannabinoids accumulate in fatty tissues, reaching peak concentrations in 4± 5 days. They are then slowly released back into other body compartments, including the brain. Because of the sequestration in fat, the tissue elimination half-life of THC is about 7 days, and complete elimination of a single dose may take up to 30 days  Maykut, 1985). Clearly, with repeated dosage, high levels of cannabinoids can accumulate in the body and continue to reach the brain. Within the brain, THC and other cannabinoids are differentially distributed. High concentrations are reached in neo- cortical, limbic, sensory and motor areas.

End quote

Quote

Tolerance has been shown to develop to many effects of cannabis including the high and many systemic effects, and a cannabis withdrawal syndrome has been clearly de- monstrated in controlled studies in both animals and man  Jones, 1983; Kouri et al, 1999). The withdrawal syndrome has simila- rities to alcohol, opiate and benzodiazepine withdrawal states and includes restlessness, insomnia, anxiety, increased aggression, anorexia, muscle tremor and autonomic ef- fects. A daily oral dose of 180 mg of THC  one or two modern, good-quality joints) for 11±21 days is sufficient to produce a well-defined withdrawal syndrome  Jones, 1983). The development of tolerance leads some cannabis users to escalate dosage, and the presence of withdrawal syndrome en- courages continued drug use. Thus, chronic cannabis use can lead to drug dependence,

End quote

And this wd syndrome

Quote

Tolerance has been shown to develop to many effects of cannabis including the high and many systemic effects, and a cannabis withdrawal syndrome has been clearly de- monstrated in controlled studies in both animals and man  Jones, 1983; Kouri et al, 1999). The withdrawal syndrome has simila- rities to alcohol, opiate and benzodiazepine withdrawal states and includes restlessness, insomnia, anxiety, increased aggression, anorexia, muscle tremor and autonomic ef- fects. A daily oral dose of 180 mg of THC  one or two modern, good-quality joints) for 11±21 days is sufficient to produce a well-defined withdrawal syndrome  Jones, 1983). The development of tolerance leads some cannabis users to escalate dosage, and the presence of withdrawal syndrome en- courages continued drug use. Thus, chronic cannabis use can lead to drug dependence,

End quote

Long term effects

Quote

There is considerable evidence, reviewed by Hall et al  1994), that performance in heavy, chronic cannabis users remains impaired even when they are not actually intoxicated. These impairments, especially of attention, memory and ability to process complex information, can last for many weeks, months or even years after cessation of cannabis use  Solowij, 1998). Whether or not there is permanent cognitive impair- ment in heavy long-term users is not clear.

End quote

I can personally say I smoke Pot every single day at college and on graduation day I quit CT. I had no ill effects and never craved it.

Smoking pot and using medical strains with high CBD are apples and oranges.  As Leslie said, there are many conditions for which cannabis has been found effective. These are, however, for the most part, not high THC strains. 

Getting high is avoided by most medical users.  Those of us who use it as medicine spend a lot of time learning how to use it properly. THC is only one cannabinoid (and the only one that is psychoactive) out of an estimated 100+, not to mention more elements in the form of terpenes and flavonoids.

Our bodies have an endocannabinoid system that enables us to readily utilize cannabis.

http://reset.me/story/beginners-guide-to-the-endocannabinoid-system/

Hi kpin99,

 

Thanks for posting this informative link.

I don't use it either, after doing the research on it.    It's up to each individual to make that choice.

 

Aston does point out some issues with cannibis in this article.  Unfortunately,  the article is quite dated (2001), and the latest cutting edge research from Israeli researchers were not available in full, at the time of the writing of the paper.

It does not read as an endorsement.  I skimmed it very quickly. 

She lists several physiological negative collateral effects in the last section

 

She does allude to some of these issues here.  (The coupling to GABAARs has been discovered by the latest research.....)

Hi dm123,

I found a link to the Ashton essay (on cannabis) in one of the many posts member Perseverance makes in this board (look under "chewing the fat") to explain the biochemistry of benzodiazepines, their actions and withdrawal. I actually detest marijuana because I get DP/DR when I smoke it and I was wondering if marijuana's mechanism of action could have an overlap with benzos (specifically its withdrawal or BWD). What I found was that there is an intersection among all three: alcohol consumption, cannabis consumption and benzos.

- All three effect opiate, serotonin and dopamine neurotransmitters, in addition to their specific transmitters,

- All three are cross tolerant (on GABA)

- All three have a withdrawal syndrome

Lastly, I found something which I had not expected to find: Ashton does not mind moderate drinking in BWD but I felt she would take umbrage to moderate cannabis use (so I felt). And I did drink while tapering and nothing happened (but, I know that in benzo land, the same thing, if repeated, could have different results.)

Lastly, I can tell that you have a background in medicine. So since Perseverance has left BB,

Please tell me, : )

1) Which theory, according to you, is the most credible for explaining BWD (down regulation, GABAAR uncoupling? non gaba actions of benzodiazapines or some other?). And what happens to the BZD receptors in these theories (if anything happens)?

2) Why do barbiturates not have a similar withdrawal? I know one potentiates, whereas the other increases the frequency of the gate through which the chloride ion passes (am I right?), but this seems to suggest to me (a layman) that BWD might not have anything to do with gaba (just as serotonin might not have anything to do with depression).

3) Tolerance in rats develops in 12 hours. So I do not think the tolerance theories that get thrown around (down regulation occurs, as in rats, and as described by one of the above theories) is the same as what we mean by tolerance in BB (which is a consequence of long-term or sufficiently chronic use).

4) Why isn’t alcohol withdrawal as sinister as BWD? Heavy alcohol withdrawal? Very heavy? (Can we treat seizures as a separate syndrome?). 

I am not a science guy and thus I could have made mistakes in comprehending Perseverance's lectures above (please correct me) and please bear with me if I do not understand your replies.

Here's a new article just out today: https://www.washingtonpost.com/lifestyle/style/cbd-is-cannabis-that-wont-get-you-high-so-why-are-so-many-people-using-it/2018/03/29/3836922a-2d2c-11e8-8ad6-fbc50284fce8_story.html?utm_term=.9f866428a0cd

The endocannabinoid system was only discovered in the mid 90s.  Ashton wouldn't have had this information when she published the Manual. 

We have to update our knowledge as it becomes available.

Yes, you are right. Ashton would not have known about stuff like anandamide, though she does hint that it might have been discovered as she was writing that essay.

But, tell me, is CBD oil of the cannabis sativa plant and that of hemp different or the same?

Hi kpin99,

 

Thanks for posting this informative link.

I don't use it either, after doing the research on it.    It's up to each individual to make that choice.

 

Aston does point out some issues with cannibis in this article.  Unfortunately,  the article is quite dated (2001), and the latest cutting edge research from Israeli researchers were not available in full, at the time of the writing of the paper.

It does not read as an endorsement.  I skimmed it very quickly. 

She lists several physiological negative collateral effects in the last section

 

She does allude to some of these issues here.  (The coupling to GABAARs has been discovered by the latest research.....)

 

Hi dm123,

 

I found a link to the Ashton essay (on cannabis) in one of the many posts member Perseverance makes in this board (look under "chewing the fat") to explain the biochemistry of benzodiazepines, their actions and withdrawal. I actually detest marijuana because I get DP/DR when I smoke it and I was wondering if marijuana's mechanism of action could have an overlap with benzos (specifically its withdrawal or BWD). What I found was that there is an intersection among all three: alcohol consumption, cannabis consumption and benzos.

 

- All three effect opiate, serotonin and dopamine neurotransmitters, in addition to their specific transmitters,

- All three are cross tolerant (on GABA)

- All three have a withdrawal syndrome

 

Lastly, I found something which I had not expected to find: Ashton does not mind moderate drinking in BWD but I felt she would take umbrage to moderate cannabis use (so I felt). And I did drink while tapering and nothing happened (but, I know that in benzo land, the same thing, if repeated, could have different results.)

 

Lastly, I can tell that you have a background in medicine. So since Perseverance has left BB,

 

Please tell me, : )

 

1) Which theory, according to you, is the most credible for explaining BWD (down regulation, GABAAR uncoupling? non gaba actions of benzodiazapines or some other?). And what happens to the BZD receptors in these theories (if anything happens)?

2) Why do barbiturates not have a similar withdrawal? I know one potentiates, whereas the other increases the frequency of the gate through which the chloride ion passes (am I right?), but this seems to suggest to me (a layman) that BWD might not have anything to do with gaba (just as serotonin might not have anything to do with depression).

3) Tolerance in rats develops in 12 hours. So I do not think the tolerance theories that get thrown around (down regulation occurs, as in rats, and as described by one of the above theories) is the same as what we mean by tolerance in BB (which is a consequence of long-term or sufficiently chronic use).

4) Why isn’t alcohol withdrawal as sinister as BWD? Heavy alcohol withdrawal? Very heavy? (Can we treat seizures as a separate syndrome?). 

 

I am not a science guy and thus I could have made mistakes in comprehending Perseverance's lectures above (please correct me) and please bear with me if I do not understand your replies.

Hi Kpin,

Thanks for your reply.  I do have a strong background in neurophysiology and chemistry, and I hope I can help you understand and answer those very pertinent questions that you have listed above.

Please note: I neither condemn nor endorse marijuana during and post Benzodiazaphine wd.  I've chosen not to use it based on my own assessments, but as many others have posted here on BB, it has indeed helped them.  I do feel that it's the lesser of 2 evils when it comes to Benzodiazaphines, but anything is better than Benzodiazaphine chronic use.  I know much more about Benzodiazaphines than marijuana.  There are others on BB who have a vast knowledge of marijuana, so I will defer to them.  However I will post some information on it in the thread link below.

I'm going to refer you to the thread that I've done the majority of my posts on.  It's also in Chewing the Fat.

It's called Can anyone explain this to a layperson?

Here's the link to it.

http://www.benzobuddies.org/forum/index.php?topic=184940.0

I do hope the administrators PIN it , so that it gets even greater visibility.

It's very very dense and packed with some of my research in the area of Benzodiazaphine wd, tolerance and kindling.  Unfortunately, it's not indexed, but you can wade through the thread or click in my profile Dm123 to pull up all the papers.  There are at least 20-25 fairly long papers in it.  I'm posting the research in the hopes that it helps us understand why we feel the way we feel.  Ultimately, if new therapeutic regimens and protocols come from it, that will be great.  It will also help you avoid things that can make Benzodiazaphine wd , tolerance, and kindling worse, and there are also strategies in there to help you heal your brain.

Regarding your excellent questions

1. I go through this in excruciating detail in the link above.  The information is a bit overwhelming, so I suggest you read a bit at a time.  Post your questions in that thread so that I can answer them, in case you do not understand anything or need further clarification.  Unfortunately, it's very complicated.  All of the mechanisms you listed above, and more, are explained in the link above.  Downreguation (changes in population density), desensitization, changes in receptor Subunit distribution (synaptic vs extrasynaptic) are just a few of the effects of chronic Benzodiazaphines on the GABAaR itself.  There are also many other collateral systems that are affected  and these are systematically presented in the papers in that link above.

2.Regarding barbiturates, could you please post some references about withdrawal.  Your layman explanation of barbiturates is correct.  From what I understand, barbiturates are terribly addictive and do have a severe withdrawal.  I did my research in this area based on historical anecdotal articles written  about famous personalities who died from overdose of the drug.  As you know, barbiturates have been around for many many decades.  Tolerance develops, and the historical articles and accounts that I've read about it paint a gruesome picture.    These accounts go back to the early 1900s, wherein users tell how the drug has enveloped them and taken over their lives, and that use has escalated.  Many inadvertently overdose.

Barbiturates also affect the glutamatergic receptors as well.

I'm sure you've read this

https://en.m.wikipedia.org/wiki/Barbiturate_dependence

We can discuss this further if you would like.

Regarding PWS and barbiturates, I would need to research if that does occur at the same frequency and intensity as it does with Benzodiazaphines.  We know PWS can occur with Benzodiazaphines, and much of the information in that link above, explains why and how this occurs.

Regarding extra cellular GABA neurotransmitter levels as being the main instigator of wd and tolerance, you are right.  It does play a role, but it's not our main issue.  However, all of these drugs, including alcohol affect presynaptic release of many neurotransmitters, including GABA.  In addition, the neurophysiology will homeostatically adjust, via feedback mechanisms, and extra cellular levels can change if there is an overstimulation of the neuron's inhibitory GABAaRs .

3. Regarding toerance.  Could you post the rat studies.  Looking back, i developed tolerance to lorazepam very very quickly, on the order of weeks.  But I so see your point.  I would need to see those rat studies, namely because the amount of Benzodiazaphine might have been a super physiological dose, and it might have been administered intravenously, etc...

4. Regarding alcohol wd, alcohol binds differently to the GABAaR, and is more than just a PAM(positive allosteric modulator) of the receptor.  Neurosteroids bind uniquely to different subunits than Benzodiazaphines as well, and are not as toxic to the receptor.

Also alcohol binds primarily to the β1 Subunit.    We know from clinical research that the alpha receptors have a much higher propensity to cause "issues" with chronic stimulation, than the beta subunits.    Benzodiazaphines bind to various alpha receptors, and ironically the most potent Benzodiazaphines bind with high affinity to various alpha receptors.  This has very strong ramifications for wd, tolerance development, kindling probability, etc.

In addition , α4s and δ (tonic) extrasynaptic receptors are affected by alcohol, and α1(but not to the degree of Benzodiazaphine modulation)

The study below is good because it explains the differences in Subunit binding affinities of Benzodiazaphines vs. alcohol.

In addition, lower alcohol levels differentially bind vs. higher levels of alcohol.(i.e. Drinking pattern plays a role)

Finally the pharmacokinetics of Benzodiazaphines vs. alcohol are different.

The alcoholics that avoid binge drinking do the best because they maintain steady state of the drug in the blood.  Binge drinkers are much more likely to develop tolerance and get kindled.  Many of us here would have been much "better" of on Valium or Librium as the initial Benzodiazaphine.  While I'd do understand that some have trouble Crossing over from a high potency Benzodiazaphine to Valium or Librium, this is due, in part to what the high potency Benzodiazaphines have done to the Subunit configuration of the GABAaRs .  Certain subunits are decompensated both regionally in the brain, and relative to extrasynaptic vs synaptic distribution.  Subunit configurations are in a sense "rearranged", and switching over to a lower potency drug will be uncomfortable.

See this reference below

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2574824/

Quote

the single channel level, ethanol enhanced the frequency of GABA-mediated channel opening events, mean open time, open time percentage, frequency of opening bursts, and mean burst duration (Tatebayashi et al., 1998).

End quote

Quote

Because GABA receptors containing the δ subunit are found in the extrasynaptic regions and are responsible for tonic inhibition, a model has emerged with ethanol selectively enhancing tonic, rather than synaptic, GABAergic transmission.

End quote

Quote

Mutant α1(S270H/L277A) mice showed more rapid recovery from the motor-impairing effects of ethanol and displayed increased anxiolytic effects of ethanol in comparison to wild-type mice (Werner et al., 2006).

End quote

Regarding marijuana, I will post my limited research in this area in the Layman's thread indicated above.

I hope this helps a bit.

EDIT ADD 3/30/18:

kpin, I just noticed that you had mentioned alcohol use during Benzodiazaphine tapering.  As far as I know, this is not supported in any detox protocols.  Could you please post where it states that it is ok to drink while tapering?    I think it was ok for you because you were on Librium to detox from alcohol itself.  So I assume you tapered both at the same time.

Consuming alcohol during a strict Benzodiazaphine taper would be counterproductive.  The affected subunits do overlap.  I'm sure there are people that have done this, but it would make an already difficult process potentially more difficult. 

 

 

It's called Can anyone explain this to a layperson?

 

Here's the link to it.

 

http://www.benzobuddies.org/forum/index.php?topic=184940.0

 

I do hope the administrators PIN it , so that it gets even greater visibility.

I will respond to you with my questions in that thread. But first I need time to absorb all the information you have given. I will send a PM to Moderator Leslie Ash straightaway, requesting that your post be pinned.

Many of us here would have been much "better" of on Valium or Librium as the initial Benzodiazaphine.  While I'd do understand that some have trouble Crossing over from a high potency Benzodiazaphine to Valium or Librium, this is due, in part to what the high potency Benzodiazaphines have done to the Subunit configuration of the GABAaRs .  Certain subunits are decompensated both regionally in the brain, and relative to extrasynaptic vs synaptic distribution.  Subunit configurations are in a sense "rearranged", and switching over to a lower potency drug will be uncomfortable.

I have seen a few others taper using librium here and they all had a painless taper. I was praying that I'd turn out to be like them and it happened. There are many members here who tapered using librium. Let's see if we can get anywhere by listing their names, doses and withdrawal experiences. I will try to collate this data, from BB and web, and post in that thread. Ashton also had a few librium taper-ers -- I'll include them. Let's see if there is a hidden message in it. I hope there is. See this post of mine.  Collating data for valium taperers would be a monumental task in this respect, so I'll pass.

kpin, I just noticed that you had mentioned alcohol use during Benzodiazaphine tapering.  As far as I know, this is not supported in any detox protocols.  Could you please post where it states that it is ok to drink while tapering?    I think it was ok for you because you were on Librium to detox from alcohol itself.  So I assume you tapered both at the same time.

I drank a couple of pegs on two social occasions. Here is Ashton on drinking:

Diets, Fluids and Exercise

Similarly with alcohol: a glass or two of wine is perfectly permissible (and even said by some to be advisable for health). Although it is important not to substitute increasing doses of alcohol for decreasing doses of benzodiazepines, there is no need to deny oneself small pleasures. Moderation is the key: there is no call to be puritanical.

I also saw one member mention that a few glasses of wine helped him in withdrawal:

Lostdog on wine

I also don't think drinking wine will extend any symptoms. I don't really have a taste for alcohol, but a glass of wine often helped take the edge off in the late afternoons when I usually got extreme anxiety. I think I only did that from about 12 to 16 months and then no longer had a need for it.

 

Coffee also helped clarify my foggy thinking in the mornings, but be really careful you don't have more than one or two because it can cause pretty extreme anxiety.

But when I reached below 5 mg librium (= 2 mg valium), I realized I could not tolerate even coffee; so drinking is now out of question. I have read that most members experience a setback when they drink. I saw that the average was 15 days of setback (or deep hangover). I had prepared myself for 15 days suffering in case my experiment backfired but that did not happen. Maybe I should not have risked it? It doesn't matter for it is history now.

I think it was ok for you because you were on Librium to detox from alcohol itself.  So I assume you tapered both at the same time.

I was an alcoholic but I quit alcohol a year before I started tapering librium (I had mixed both for ten years and sometime during this period my doctor had switched me from 0.5 mg K to 20 mg librium because of my alcoholism). I drank a couple of times while tapering librium just as an experiment.

3. Regarding toerance.  Could you post the rat studies.  Looking back, i developed tolerance to lorazepam very very quickly, on the order of weeks.  But I so see your point.  I would need to see those rat studies, namely because the amount of Benzodiazaphine might have been a super physiological dose, and it might have been administered intravenously, etc...

https://www.ncbi.nlm.nih.gov/pubmed/8818332

Abstract

1. Chronic benzodiazepine treatment of rat cerebellar granule cells induced a transient down-regulation of the gamma-aminobutyric acidA (GABAA) receptor alpha 1 subunit protein, that was dose-dependent (1 nM-1 microM) and prevented by the benzodiazepine antagonist flumazenil (1 microM). After 2 days of treatment with 1 microM flunitrazepam the alpha 1 subunit protein was reduced by 41% compared to untreated cells, which returned to, and remained at, control cell levels from 4-12 days of treatment. Chronic flunitrazepam treatment did not significantly alter the GABAA receptor alpha 6 subunit protein over the 2-12 day period. 2. GABA treatment for 2 days down-regulates the alpha 1 subunit protein in a dose-dependent (10 microM-1 mM) manner that was prevented by the selective GABAA receptor antagonist bicuculline (10 microM). At 10 microM and 1 mM GABA the reduction in alpha 1 subunit expression compared to controls was 31% and 66%, respectively. 3. The flunitrazepam-induced decrease in alpha 1 subunit protein is independent of GABA, which suggests that it involves a mechanism distinct from the GABA-dependent action of benzodiazepines on GABAA receptor channel activity. 4. Simultaneous treatment with flunitrazepam and GABA did not produce an additive down-regulation of alpha 1 subunit protein, but produced an effect of the same magnitude as that of flunitrazepam alone. This down-regulation induced by the combination of flunitrazepam and GABA was inhibited by flumazenil (78%), but unaffected by bicuculline. 5. The flunitrazepam-induced down-regulation of alpha 1 subunit protein at 2 days was completely reversed by the protein kinase inhibitor staurosporine (0.3 microM). 6. This study has shown that both flunitrazepam and GABA treatment, via their respective binding sites, caused a reduction in the expression of the GABAA receptor alpha 1 subunit protein; an effect mediated through the same neurochemical mechanism. The results also imply that the benzodiazepine effect is independent of GABA, and that the benzodiazepine and GABA sites may not be equally coupled to the down-regulation process, with the benzodiazepine site being the more dominant. The biochemical mechanism underlying the benzodiazepine-mediated down-regulation of the alpha 1 subunit protein seems to involve the activity of staurosporine-sensitive protein kinases.

Can you tell me if this sentence from the above study has any significance?

The results also imply that the benzodiazepine effect is independent of GABA, and that the benzodiazepine and GABA sites may not be equally coupled to the down-regulation process, with the benzodiazepine site being the more dominant. The biochemical mechanism underlying the benzodiazepine-mediated down-regulation of the alpha 1 subunit protein seems to involve the activity of staurosporine-sensitive protein kinases.

 

 

It's called Can anyone explain this to a layperson?

 

Here's the link to it.

 

http://www.benzobuddies.org/forum/index.php?topic=184940.0

 

I do hope the administrators PIN it , so that it gets even greater visibility.

 

I will respond to you with my questions in that thread. But first I need time to absorb all the information you have given. I will send a PM to Moderator Leslie Ash straightaway, requesting that your post be pinned.

 

Many of us here would have been much "better" of on Valium or Librium as the initial Benzodiazaphine.  While I'd do understand that some have trouble Crossing over from a high potency Benzodiazaphine to Valium or Librium, this is due, in part to what the high potency Benzodiazaphines have done to the Subunit configuration of the GABAaRs .  Certain subunits are decompensated both regionally in the brain, and relative to extrasynaptic vs synaptic distribution.  Subunit configurations are in a sense "rearranged", and switching over to a lower potency drug will be uncomfortable.

 

I have seen a few others taper using librium here and they all had a painless taper. I was praying that I'd turn out to be like them and it happened. There are many members here who tapered using librium. Let's see if we can get anywhere by listing their names, doses and withdrawal experiences. I will try to collate this data, from BB and web, and post in that thread. Ashton also had a few librium taper-ers -- I'll include them. Let's see if there is a hidden message in it. I hope there is. See this post of mine.  Collating data for valium taperers would be a monumental task in this respect, so I'll pass.

 

kpin, I just noticed that you had mentioned alcohol use during Benzodiazaphine tapering.  As far as I know, this is not supported in any detox protocols.  Could you please post where it states that it is ok to drink while tapering?    I think it was ok for you because you were on Librium to detox from alcohol itself.  So I assume you tapered both at the same time.

 

I drank a couple of pegs on two social occasions. Here is Ashton on drinking:

 

Diets, Fluids and Exercise

Similarly with alcohol: a glass or two of wine is perfectly permissible (and even said by some to be advisable for health). Although it is important not to substitute increasing doses of alcohol for decreasing doses of benzodiazepines, there is no need to deny oneself small pleasures. Moderation is the key: there is no call to be puritanical.

 

I also saw one member mention that a few glasses of wine helped him in withdrawal:

 

Lostdog on wine

 

I also don't think drinking wine will extend any symptoms. I don't really have a taste for alcohol, but a glass of wine often helped take the edge off in the late afternoons when I usually got extreme anxiety. I think I only did that from about 12 to 16 months and then no longer had a need for it.

 

Coffee also helped clarify my foggy thinking in the mornings, but be really careful you don't have more than one or two because it can cause pretty extreme anxiety.

 

But when I reached below 5 mg librium (= 2 mg valium), I realized I could not tolerate even coffee; so drinking is now out of question. I have read that most members experience a setback when they drink. I saw that the average was 15 days of setback (or deep hangover). I had prepared myself for 15 days suffering in case my experiment backfired but that did not happen. Maybe I should not have risked it? It doesn't matter for it is history now.

 

I think it was ok for you because you were on Librium to detox from alcohol itself.  So I assume you tapered both at the same time.

 

I was an alcoholic but I quit alcohol a year before I started tapering librium (I had mixed both for ten years and sometime during this period my doctor had switched me from 0.5 mg K to 20 mg librium because of my alcoholism). I drank a couple of times while tapering librium just as an experiment.

Hi Kpin,

Thanks for the references and additional information.  I'm also tapering with Librium.  I'm at around the last 10%, and at times it's been difficult, but the windows are incredible, and I'm much better after the crossover.

I see that you are on the last  2.5 mg correct?

I did not know that Ashton felt it ok to drink low alcohol during taper, but she is clear that one needs to be careful substituting alcohol for the taper dosage decrease.  It seems to me that this can be a slippery slope.  Many of us started with small amounts of Benzodiazaphines, and this escalated as tolerance set in.  Downregulation and desensitization of the GABAaRs is a continuous degenerative process.    I will reply to the citation you posted below separately.  There is no doubt in my mind that downregualtion begins very quickly in susceptible individuals.  However , some individuals do not experience downregulation and desensitization after even very very long long periods of use.  The citation below is quite old and they do understand the processes involved in downregulation and Subunit reconfiguration much better now.  The citation below does refer to changes in phosphorylation, which I do get into on the Layman's thread that I referred you to.  I also get into differences between downreguation (i.e., decreases inreceptor population ) as opposed to desensitization of the receptor which can be due to changes in Subunit configuration.    The receptors undergo 2 processes which facilitate these changes, endocytosis and exocytosis which I get into in the Layman's thread.

You had a good doctor, in that he switched you from clonazepam to Librium.  It saved you a lot of misery.

I can understanding why people can experience a setback when sporadically drinking because the alcohol is disturbing the steady state.  If you are going to drink, the worst thing to do is binge drink.

I do understand the threshold effect you are hitting at 5 mg Librium

You should continue with a symptom based taper and hold until your excitatory and inhibitory systems rebalance.  It's normal to experience hypersensitivity to caffeine and other stimulants when tapering , especially at the low dosages.

If you can do it, I would hold off on the coffee until your nervous system stabilizes.

Yes, I am at 2.5 mg librium (1.9 mg librium to be precise). I have been on a hold for a month because benzo belly is intolerable. I will wait a few more weeks to see if I get any relief but I am not in a hurry.

I have stopped coffee and switched to tea. I agree drinking is not a good idea in taper, and certainly not binge drinking. There are a lot of drinking-in-taper catastrophe stories in BB.

I will now go over and read your thread in "chewing the fat" (the one for layman).

Wish the rest of your taper is painless. We both are at roughly the same stage in taper.

3. Regarding toerance.  Could you post the rat studies.  Looking back, i developed tolerance to lorazepam very very quickly, on the order of weeks.  But I so see your point.  I would need to see those rat studies, namely because the amount of Benzodiazaphine might have been a super physiological dose, and it might have been administered intravenously, etc...

 

https://www.ncbi.nlm.nih.gov/pubmed/8818332

 

Abstract

1. Chronic benzodiazepine treatment of rat cerebellar granule cells induced a transient down-regulation of the gamma-aminobutyric acidA (GABAA) receptor alpha 1 subunit protein, that was dose-dependent (1 nM-1 microM) and prevented by the benzodiazepine antagonist flumazenil (1 microM). After 2 days of treatment with 1 microM flunitrazepam the alpha 1 subunit protein was reduced by 41% compared to untreated cells, which returned to, and remained at, control cell levels from 4-12 days of treatment. Chronic flunitrazepam treatment did not significantly alter the GABAA receptor alpha 6 subunit protein over the 2-12 day period. 2. GABA treatment for 2 days down-regulates the alpha 1 subunit protein in a dose-dependent (10 microM-1 mM) manner that was prevented by the selective GABAA receptor antagonist bicuculline (10 microM). At 10 microM and 1 mM GABA the reduction in alpha 1 subunit expression compared to controls was 31% and 66%, respectively. 3. The flunitrazepam-induced decrease in alpha 1 subunit protein is independent of GABA, which suggests that it involves a mechanism distinct from the GABA-dependent action of benzodiazepines on GABAA receptor channel activity. 4. Simultaneous treatment with flunitrazepam and GABA did not produce an additive down-regulation of alpha 1 subunit protein, but produced an effect of the same magnitude as that of flunitrazepam alone. This down-regulation induced by the combination of flunitrazepam and GABA was inhibited by flumazenil (78%), but unaffected by bicuculline. 5. The flunitrazepam-induced down-regulation of alpha 1 subunit protein at 2 days was completely reversed by the protein kinase inhibitor staurosporine (0.3 microM). 6. This study has shown that both flunitrazepam and GABA treatment, via their respective binding sites, caused a reduction in the expression of the GABAA receptor alpha 1 subunit protein; an effect mediated through the same neurochemical mechanism. The results also imply that the benzodiazepine effect is independent of GABA, and that the benzodiazepine and GABA sites may not be equally coupled to the down-regulation process, with the benzodiazepine site being the more dominant. The biochemical mechanism underlying the benzodiazepine-mediated down-regulation of the alpha 1 subunit protein seems to involve the activity of staurosporine-sensitive protein kinases.

 

Can you tell me if this sentence from the above study has any significance?

 

The results also imply that the benzodiazepine effect is independent of GABA, and that the benzodiazepine and GABA sites may not be equally coupled to the down-regulation process, with the benzodiazepine site being the more dominant. The biochemical mechanism underlying the benzodiazepine-mediated down-regulation of the alpha 1 subunit protein seems to involve the activity of staurosporine-sensitive protein kinases.

Hi kpin

Thanks for the citation.  As I mentioned above it's very old, but they were on the right track.  They ultimately pointed to changes in phosphorylation ("protein kinases") which affect what is called receptor trafficking .  Receptor trafficking refers to how receptors are absorbed (endocytosis) and how they re-emerge at the neuron membrane surface (exocytosis) based on what is going on outside of the neuron.  If there is excessive potentiation of a receptor at particular subunits, the receptor tends to downregulate the population density of those receptors with those subunits and repopulate with GABAaRs with different subunits that are potentially less sensitive to the endogenous GABA neurotransmitter and/or the Benzodiazaphine.  Changes in phosphorylation are intracellular processes which are behind neuro-kindling, downregulation, etc.

The drug concentrations used are "normal".  For reference here are some affinities of various Benzodiazaphines for the GABAAR.  I'm working in trying to find a reliable source of affinities of the various Benzodiazaphines at the Subunit level, but this data is hard to find.

Here is the table for your reference.  You can see that the concentrations in the study were in nM to microM.  The GABA concentrations were much higher (up to mill-M range), but I don't know what a normal GABA concentration is.

(In this table you can see just how weak Librium is relative to the high potency Benzodiazaphines, Librium is at the bottom.  I will post this table on the Layman's thread as well)

triazolam 1.31 umol

alprazolam 1.38 umol

clonazepam 1.43 umol

flunitrazepam 1.60 umol

lorazepam 2.65 umol

loprazolam 2.90 umol

lormetazepam 3.58 umol

eszopiclone 4.24 umol

estazolam 4.73 umol

bromazepam 14.61 umol

quazepam 17.06 umol

zaleplon 19.65 umol

zopiclone 21.22 umol

nitrazepam 30.48 umol

diazepam 32.67 umol

medazepam 33.23 umol

nordazepam 33.25 umol

clorazepate 41.27 umol

prazepam 41.56 umol

flurazepam 47.08 umol

halazepam 51.03 umol

ketazolam 53.69 umol

clobazam 59.90 umol

zolpidem 59.90 umol

temazepam 63.90 umol

oxazepam 67.00 umol

chlordiazepoxide 75.00 umol

Keep in mind, this is the general affinity of the Benzodiazaphine for the GABAAR at the Benzodiazaphine binding site, and I don't have the information at the Subunit level.  We do know that the Benzodiazaphine binding site is at α and γ and GABA at α and β, but Benzodiazaphines also have affinity to β subunits as well.

I mention this because the α1  is common to both, hence the purpose of the study: to differentiate between the downregulation effects of Benzodiazaphines vs endogenous GABA . 

They do this via a Benzodiazaphine, GABA, a GABA antagonist, and a Benzodiazaphine antagonist.

The Benzodiazaphine incites a particular protein kinase intracellularly, that adversely affects the α1 Subunit (downregulates it) in a way that natural endogenous GABA does not.  They use antagonists to selectively block the effects of each to isolate what is causing this downregulation of the α1.

See also point 4 below

Quote

Simultaneous treatment with flunitrazepam and GABA did not produce an additive down-regulation of alpha 1 subunit protein, but produced an effect of the same magnitude as that of flunitrazepam alone. This down-regulation induced by the combination of flunitrazepam and GABA was inhibited by flumazenil (78%), but unaffected by bicuculline.

End quote

So GABA incites downregulation of α1 via a completely different process than that of the Benzodiazaphine. The Benzodiazaphine's intracellular effect on the neuron is unique and completely uncoupled from the effect that GABA has on the neuron.  Using the GABA antagonist, as indicated in the quote above does not reverse this effect because of the discrete process involved.

In real life, if GABA concentrations rose to a level that started downregulating α1, the neurons acting as a collective neural circuit would homeostatically adjust, and the presynaptic release of GABA would be throttled down, to alleviate the α1 downreguation.  Injecting GABA directly into the extracelluar compartment does not happen in real life, but it did serve a purpose in this study. (Brain blood barrier even blocks GABA supllements from hitting the brain)

When we ingest Benzodiazaphines, it is a completely different story.  Natural homeostatic plasticity is completely messed up, and the neural circuits will not be able to adjust after a certain point, as the α1 slowly and continually downregulates further and further.  These kinases that are involved in the aberrant phosphorylation of the receptor are not natural.  Eventually , the neural circuit can no longer accommodate and we enter a symptomatic tolerance.  This can take weeks, months or even years.    I haven't presented the material on homeostatic plasticity and neural circuits yet, in the Layman's thread.   

You are correct.  The process of downregulation can occur very rapidly, but the neural circuit can accommodate quite a bit of stress (Benzodiazaphine) before physiological function deteriorates and tolerance symptoms emerge.

I hope this helps.  The takeaway is that Benzodiazaphines are unique in their detrimental effects on the receptor configuration, as opposed to naturally occurring endogenous GABA

Yes, I am at 2.5 mg librium (1.9 mg librium to be precise). I have been on a hold for a month because benzo belly is intolerable. I will wait a few more weeks to see if I get any relief but I am not in a hurry.

 

I have stopped coffee and switched to tea. I agree drinking is not a good idea in taper, and certainly not binge drinking. There are a lot of drinking-in-taper catastrophe stories in BB.

 

I will now go over and read your thread in "chewing the fat" (the one for layman).

 

Wish the rest of your taper is painless. We both are at roughly the same stage in taper.

I agree. Prevent symptoms and let the body heal.

See my post above as well.  I posted it just now.

dm123,

I get your point about barbiturates withdrawal being as severe as benzo withdrawal. I suppose because there was no Internet then, or an Ashton clinic, protracted withdrawals from barbiturates were not recognized (and were treated as another psychiatric disorder). But, like benzodiazepines, do you think barbiturates too had/have a "tolerance withdrawal" profile? As in inducing symptoms they are supposed to treat, like depression and anxiety.

dm123,

 

I get your point about barbiturates withdrawal being as severe as benzo withdrawal. I suppose because there was no Internet then, or an Ashton clinic, protracted withdrawals from barbiturates were not recognized (and were treated as another psychiatric disorder). But, like benzodiazepines, do you think barbiturates too had/have a "tolerance withdrawal" profile? As in inducing symptoms they are supposed to treat, like depression and anxiety.

Hi kpin,

There's not a lot of new research being done with barbiturates, as they have been phased out, for the most part, in outpatient psychological medical care in the USA.  I don't know if they are still widely prescribed in other countries, but I would assume not.  Perhaps someone from the European or Canadian region could comment on that.  I know that they are used for seizure control, but we are not discussing that here.

It's safe to assume that tolerance withdrawal does develop.  Many of the deaths that I researched from anecdotal archives were accidental overdoses.  I guess if there's one redeeming quality about Benzodiazaphines, it's that they are difficult to overdose on (by themselves, i.e. No opiates, etc involved). 

I haven't researched barbiturate effects on neurophysiology, just Benzodiazaphines, so I don't know if the tolerance withdrawal would be paradoxical as it is for Benzodiazaphines.  Benzodiazaphines induce widespread changes in the core neurophysiology and in the endocrine systems, and ultimately disrupt neurotransmitter homeostasis.  Collateral effects on dopamine, serotonin, acetylcholine, cortisol, etc  do occur with Benzodiazaphines.  We know this not only because of the clinical studies, but because GPCRs do couple to and modulate GABAaRs.  So the systems systems are intertwined.  The clinical research is clear on this.  Since I haven't researched barbiturates in the same context i cannot say for sure how these collateral systems are affected, but some of the older clinical studies from around 1990s-early 2000s do include barbiturates in their test studies.    Sometimes, depending on what is being studied, there are discrete differences between Benzodiazaphines and barbiturates.

But on the whole, the anecdotal evidence would have me believe that tolerance wd does eventually occur, and that the symptoms are most likely paradoxical.

Phenobarbital has a long half life so it could perhaps be used as a taper drug, but it affects glutamatergic receptors as well, and i don't know how that would factor into a successful taper.  Given my personal experience with Benzodiazaphines, I want to get as far away from this junk drug as possible, and phenobarbital seems to be going in the wrong direction.

https://www.rxlist.com/phenobarbital-drug.htm

Quote

Phenobarbital has a plasma half-life of 53 to 118 hours (mean: 79 hours). For children and newborns the plasma half-life is 60 to 180 hours (mean: 110 hours). (Half-life values were determined for newborn age being defined as 48 hours or less.)

End quote

The long half life might reduce the propensity of  neuro-kindling developing , but tolerance wd and neuro-kindling are different from a physiological perspective.

About barbiturates: it was known that barbiturates were dangerous because of their overdose potential. Likely, combining a barb with an opiate or alcohol posed a much more acute danger than a benzo.

So I'm inclined that barbiturates were not prescribed at rediculously high doses, and that problems with barbs were taken more seriously.

The 'benzos are safe', horrible.

Yes, you are right. Ashton would not have known about stuff like anandamide, though she does hint that it might have been discovered as she was writing that essay.

 

But, tell me, is CBD oil of the cannabis sativa plant and that of hemp different or the same?

CBD (cannabidiol) is the same compound in both varieties.  However, cannabis-derived CBD oil is thought to be more effective due to the additional cannabinoids, terpenes and flavonoids. 

Someone quoted earlier about why Ashton said we shouldn't use marijuana.  Two of the reasonings were due to addiction and withdrawal from marijuana.  This is where her information is not updated.  Years ago, it would have been inconceivable to give an addict marijuana to get off of other drugs, because as Ashton states, you could be trading one addiction for another.  However, many recent studies have shown that not only is marijuana NOT a gateway drug, but it can be effectively used to get people off of harder drugs, and then can be stopped (or continued) as needed.  For the majority of people over the age of 25, the only withdrawal smoking marijuana has is a couple of days of insomnia and irritability (Yes, there are some exceptions).  There are actual rehab centers opening up now using marijuana to get people off of other drugs, and are finding this is actually one of the best methods for keeping people off.  Also, a study from canada showed that almost 50% of people were able to stop using benzos once they started marijuana therapy.  There is also a facebook group that deals with marijuana and getting off of benzos that has over 1500 members, and many of them smoked through withdrawal and healed. 

Again, everyone is different, and people have been set back by both marijuana and CBD.  However, considering quite a few people actually get relief from it, I don't think people are trying to go against Ashton, I think there is just more knowledge out there regarding marijuana and different strains available.

Also: as a side note back to the whole "everyone is different", many of the supplements Ashton says to stay away from (passion flower, kava, chamomile, etc) have set many people back, but others have used these supplements and found great relief.  This isn't to say Ashton was wrong - I see people seriously set back by them all the time.  But others have used them, gotten relief, and still healed.

Yes, you are right. Ashton would not have known about stuff like anandamide, though she does hint that it might have been discovered as she was writing that essay.

 

But, tell me, is CBD oil of the cannabis sativa plant and that of hemp different or the same?

 

CBD (cannabidiol) is the same compound in both varieties.  However, cannabis-derived CBD oil is thought to be more effective due to the additional cannabinoids, terpenes and flavonoids.

https://www.medicaljane.com/2015/01/14/the-differences-between-hemp-and-cannabis/

Hemp Oil contains CDB (cannabidiol), and different levels of THC (including low, legal levels - depending on the exact plant harvested). The best Hemp oils include the whole cannibis plant, and so will include hemp oil as well.

Hemp seed oil is made from just the seeds of the cannabis plant and does NOT have any CDB.