Rizzo The Nihilizo

Friday, October 27, 2006

Opiate and (meth)Amphetamine Tolerances: Reduction, Prevention, Information:

We all know how much tolerance sucks; it will burn holes in your pockets, prevents you from getting as high as you used to, and increases the chance you're going to overdose. Well, I'm just here to let you know it doesn't have to be like that. There is hope to stop yourself from gaining tolerance, and to even completely reverse it to the point where you're getting as high as you did the first time. Do you remember the first time you got high on your opiate/opiod of choice, or the first time you got spun as fuck on meth/amps? It was fucking beautiful, huh?

NDMA antagonists have been shown to reduce tolerance to morphine:

Co-administration of dextromethorphan, memantine or MRZ 2/579 between tests 1 and 2 dose-dependently (5-10 mg/kg) inhibited the development of morphine tolerance.

Although this study shows DXM along with memantine stops a user from gaining morphine tolerance, there is some evidence that DXM alone can stop an opiate tolerance and maybe even reverse it. Also, even if DXM is not very powerful at directly reducing tolerance without another NMDA antagonist, it can certainly potentiate the effects of opiates, and reduces the negative effects of them:

Preclinical and double-blind single-dose placebo-controlled studies demonstrated that MorphiDex (MS:DM), a 1:1 ratio of morphine sulfate (MS) to dextromethorphan hydrobromide (DM), provides significantly greater analgesia than an equal dose of immediate release MS, with a faster onset, and a duration of > or = 8 h. The analgesic effect of MS:DM compared to MS was evaluated in 2 double-blind, multiple-dose studies in 321 patients with cancer and other chronic pain: a crossover study that consisted of two 2-wk periods and a 4-wk parallel study. As specified in the study protocols, patients took sufficient MS or MS:DM to achieve satisfactory pain control. In the crossover study, the MS:DM group required half as much morphine as the MS group to achieve satisfactory pain control (80 mg and 162 mg, respectively). The interval between doses and the time from the last dose of the day to the first dose of the next day were significantly longer for MS:DM compared to MS. In the parallel study, MS:DM also provided pain control at a significantly lower dose. After four weeks of treatment, the mean daily dose of MS increased, while there was little change in the MS:DM mean daily dose (P = 0.025) to maintain satisfactory pain control. More patients preferred MS:DM to run-in MS than preferred MS to run-in MS (P = 0.026). The addition of DM to MS did not increase the incidence of adverse events, which were those commonly associated with opioid use. These studies confirm that MS:DM provides satisfactory pain relief but at a significantly lower morphine daily dose.

From here.

Note that DXM is not the best choice for reducing tolerance, it is just the cheapest and most available. Do not think that a "stronger" dissociative like ketamine or PCP will work better, because it is likely that DXM's tolerance reducing ability is linked to the specific sigma receptors with which it is an agonist of. NMDA antagonists also reduce tolerance to amphetamine. It should be noted that some doses of NMDA antagonists will only stop tolerance, not reverse it:

A rat warm-water tail-withdrawal procedure was used to examine the effects of chronic administration of the competitive NMDA receptor antagonist LY235959 in morphine tolerant rats. Morphine dose-dependently increased tail-withdrawal latencies from 55 degree C water. When morphine (10 mg/kg) was administered twice-daily for 7 days, the morphine dose-effect curves shifted 0.3-0.5 log unit to the right. When morphine was administered for an additional 7 days, the morphine dose-effect curve shifted 0.4 log unit further to the right. Co-administration of LY235959 (1, 3, 10 mg/kg) along with morphine prevented the development of tolerance observed during the second week of chronic morphine administration. Although the highest dose of LY235959 (10 mg/kg) partially reversed tolerance in five of seven rats, tolerance was not reversed by lower doses of LY235959. These data suggest that NMDA receptor antagonists may effectively prevent the progressive development of morphine tolerance at doses that are not sufficient to reverse pre-established morphine tolerance.

From here.

Here's an extremely helpful thread from bluelight:

Amphetamine tolerance is caused by excess Ca++ influx through the NMDA receptor gated calcium channels on the outer membranes of the dopamine cells bodies in the ventral tegental area, one of two areas in the brain with concentrations of dopamine producing neurons.

As alluded to above, taking an appropriate NMDA (partial) antagonist will prevent the development of a tolerance for the effects of an amphetamine or amphetamine-like stimulant. Also, by preventing excess Ca++ influx into the neuron, an NMDA antagonist will prevent associated brain alterations and damage (excitotoxicity).

Studies have indicated that amphetamine tolerance is prevented by exogenous or endogenous agents that are able to inhibit excess Ca++ influx into the neuron through the gated calcium channels on the neuronal membrane that have NMDA subtype glutamate receptors .Glutamate , the body’s major excitatory neurotransmitter, opens the gated calcium ion channels upon attaching to the NMDA receptor. A number of other receptors are also expressed on these calcium channels, which, when stimulated, either facilitate or inhibit glutamate’s action.

It is also important that agents that inhibit calcium channel activity not also cause deficient Ca++ influx. For example, ketamine is a full NMDA receptor antagonist, that prevents excess Ca++ influx and amphetamine tolerance. But being a full NMDA antagonist, ketamine in excessive doses results in deficient Ca++ influx. This could be one of the reasons it leaves K-user in a state of disassociation.

So, basically you can stop amphetamine tolerance and even reduce it if you can stop the Ca++ influx. How can you do this? Quite easily, actually. From the same post that I quoted earlier:

Magnesium is also an NMDA antagonist. Most people are deficient in magnesium, and stress reduces magnesium levels. Whether or not one takes amphetamines, magnesium supplementation is very important for mood, general well-being and keeping stress levels under control. It is also important to take magnesium in efficient form, with adequate bioavailability. The best type is magnesium glycinate (chelated) with bioavailability at around 80%. Second best is magnesium carbonate with (I don't remember exactly) bioavailability at little above 30%. Supplemented magnesium should be at 500 mg/day level. Also there is a study which shows that children who use amphetamine-type stimulants have bad magnesium/calcium balance. Calcium levels stay the same with amphetamine usage, but magnesium levels drop.

There are a few theories regarding just how exactly NMDA antagonists are able to reduce tolerance. One of these ideas, regarding neuroplasticity , is the idea that NMDA receptors are responsible for tolerance, physical dependence, and sensitization, and so thusly NMDA antagonists are able to reduce and prevent tolerance:

RESULTS: The effects of NMDA receptor antagonists on the development of tolerance to opiate analgesia and the development of opiate physical dependence do not appear to be due to confounding behavioral effects produced by high doses of NMDA receptor antagonists, "side-effects" of a particular drug or drug class, blockade of associative learning processes, or state-dependency. Results on tolerance and sensitization to the locomotor effects of morphine are more mixed and controversial; however, there is evidence suggesting that NMDA receptor antagonists may inhibit these phenomena in a similar manner. CONCLUSIONS: NMDA receptor antagonists appear to inhibit the neural plasticity underlying some forms of opiate tolerance, sensitization and physical dependence, suggesting that NMDA receptors are involved in the development of these drug-induced changes in behavior. Further research will help to determine the neural mechanisms responsible for these phenomena, and the therapeutic potential for drugs acting on the NMDA receptor complex in the treatment of pain and addiction.

Taken from here.

For those of you in extreme pain daily, or just most of the time, I highly sympathize with you, as I have my own chronic pain problems. However, there is evidence to suggest that hyperalgesia is related to opiate tolerance, the idea of which will most likely not surprise some of you who are in pain and have a huge natural or perhaps "unnatural" opiate tolerance:

A model proposing that N-methyl-D-aspartate (NMDA) receptor and opioid receptor mechanisms overlap and interact within the same dorsal horn nociceptive neurons makes several predictions. First, hyperalgesia should be associated with opioid tolerance. Second, both hyperalgesia and tolerance to opioid-analgesia should be blocked by an NMDA-receptor antagonist. Results from our laboratory and others support these predictions and point to several clinical implications. One is that, in addition to preventing tolerance and dependence, combining NMDA-receptor antagonists with both opioid and nonopioid analgesics may increase their analgesic potency. Preclinical animal studies demonstrate these advantages and underscore the practicality of the combined administration of nontoxic NMDA-receptor antagonists with various types of analgesic drugs.

Taken from here.

This study is suggesting that NDMA antagonists are able to reduce and prevent tolerance because opiate receptors and NMDA receptors overlap in their mechanisms. If one has an idea of how NDMA receptors and opiate receptors work, this makes sense:

The signal from opioid receptor activation is transduced through ion channels for potassium, calcium, and enzyme systems in the cytosol and cell membrane (protein kinase C, adenylate cyclase, phospholipase A2, nitric oxide synthase, and possibly metabotropic glutamate receptors). Analgesia occurs as intracellular K+ increases, Ca++ decreases, and cyclic AMP (cAMP) decreases.

From here.

This is starting to make sense now, isn't it? There is further proof that opiate tolerance(and amphetamine tolerance as well) has something strongly to do with a Ca++ influx. This study suggests that nimodipine, a calcium channel blocker, can increase the analgesic effects of morphine and/or reduce tolerance:

The ability of nimodipine, a calcium-channel blocker, to enhance morphine analgesia and/or modify the development of tolerance was studied in patients with cancer pain who had needed successive increments of morphine for periods ranging from 21 to 780 days. Assessment of daily morphine consumption was the primary effect parameter. Nimodipine succeeded in reducing the daily dose of morphine in 16 of 23 patients (oral, n = 13; intrathecal, n = 3), and failed to modify it in 2 patients. Total oral daily dose was reduced by nimodipine (120 mg/day) from 282.6 +/- 47.7 mg to 158.7 +/- 26.2 mg (n = 15, P < n =" 3)" n =" 2).">

Specifically regarding amphetamines, amphetamines seem to throw off the magnesium-calcium ratio (the two are heavily related and are almost always absorbed together):

Dextroamphetamine can increase blood levels of magnesium, which causes significant lowering of the calcium to magnesium ratio in the blood. The change in this ratio may in part explain the effectiveness of stimulants like dextroamphetamine in hyperactive boys.

1 Another magnesium-amphetamine interaction involves supplements of magnesium hydroxide, which are known to cause retention of amphetamines in the body.

2 This could theoretically result in increased blood levels of these drugs. Finally, animal studies have suggested that magnesium supplements can increase learning and enhance the behavioral response to stimulants.

3 For these reasons, the use of magnesium along with amphetamines may enhance the effectiveness of these drugs in the treatment of ADD, but controlled studies of this possibility are needed.

References:

1. Schmidt ME, Kruesi MJ, Elia J, et al. Effect of dextroamphetamine and methylphenidate on calcium and magnesium concentration in hyperactive boys. Psychiatry Res 1994;54:199–210.

2. Hurwitz A. Antacid therapy and drug kinetics. Clin Pharmacokinet 1977;2:269–80.

3. Reviewed in Schmidt ME, Kruesi MJ, Elia J, et al. Effect of dextroamphetamine and methylphenidate on calcium and magnesium concentration in hyperactive boys. Psychiatry Res 1994;54:199–210.

In conclusion, while there are many theories regarding opiate/amphetamine tolerance and the relate to NMDA antagonists/Ca++ influx(et cetera), there is no concrete idea of the "why" or the "how". There are some basic ideas, but the for those of you not interested in the science of it all, and would rather just focus on the practical purposes, there is plenty of information on lowering and stopping tolerances. This is by no means meant to be an end-all post, but rather a general and basic primer for tolerance. There will be new and better information coming out all the time, so be sure to research this yourself.

Love,

-Rizzo

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Articles of Interest

Here are a few articles of interest:

Cheney the water-board-loving-fascist:


WASHINGTON - Vice President Dick Cheney has confirmed that U.S. interrogators subjected captured senior al-Qaida suspects to a controversial interrogation technique called "water-boarding," which creates a sensation of drowning.

Cheney indicated that the Bush administration doesn't regard water-boarding as torture and allows the CIA to use it. "It's a no-brainer for me," Cheney said at one point in an interview.

Cheney's comments, in a White House interview on Tuesday with a conservative radio talk show host, appeared to reflect the Bush administration's view that the president has the constitutional power to do whatever he deems necessary to fight terrorism.

Ignorant Evangelical "Christians" (hah!) show amazingly misinformed support for the murdeous Israel machine. When will these people wake up? Jesus was about love and peace, not about hate, violence, and war! Turn the other cheek, damnit!

ASHDOD, Israel - After 35 days at sea, a group of American evangelicals traveling on a creaky World War II-era cargo ship landed in Israel.

Israel on a solidarity mission only to run aground in red tape, with long delays in unloading their cargo of clothes, toys and medical supplies.

Still, the crew was unfazed Thursday, keeping a positive attitude in a demonstration of the growing alliance between evangelical Christians and the Jewish state.

"The Bible says, 'Who blesses Israel will be blessed,'" said Don Tipton, the group's leader. "We believe that."

The Spirit of Grace steamed into the Israeli port of Ashdod in early October from Louisiana, flying an American flag and a huge banner reading "Jehovah" in Hebrew letters. Three weeks later, the ship is still docked, its 900-ton load of goods bound for local charities stuck on board as the gears of Israeli bureaucracy slowly turn.

And last, but not least, an article about an ex-CIA and Marine Intelligence officer 9/11 whistleblower. Very interesting read, IMO.

An important story that broke over the weekend and may not have been widely picked up was that another former US Intelligence insider has turned whistleblower and concedes that the 9/11 attacks represented a "Neoconservative Neo-Nazi Coup D'etat".

In a review of Webster Tarpley's 9/11 Synthetic Terror: Made in USA, for Amazon, Steele contends that the book is the "strongest of the 770+ books I have reviewed"

Steele goes on:

"I am forced to conclude that 9/11 was at a minimum allowed to happen as a pretext for war (see my review of Jim Bamford’s “Pretext for War”), and I am forced to conclude that there is sufficient evidence to indict (not necessarily convict) Dick Cheney, Karl Rove and others of a neo-conservative neo-Nazi coup d’etat and kick-off of the clash of civilizations (see my review of “Crossing the Rubicon” as well as “State of Denial”). Most fascinatingly, the author links Samuel Huntington, author of “Clash of Civilizations” with Leo Strauss, the connecting rod between Nazi fascists and the neo-cons."

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Thursday, October 26, 2006

US Troops To Government: No More War

WASHINGTON (Reuters) - More than 200 active duty U.S. armed service members, fed up with the war in Iraq, have joined an unusual protest calling for withdrawal of U.S. troops from the country, organizers said on Wednesday.

The campaign, called the Appeal for Redress from the War in Iraq, is the first of its kind in the Iraq war and takes advantage of Defense Department rules allowing active duty troops to express personal opinions to members of Congress without fear of retaliation, organizers said.

Link

Well, this revelation brings a whole new meaning to the much over-used slogan by SUV drivers everywhere in America, "Support the troops!" The cognitive dissonance that must be going on in the war-hawk mainstream American public has likely reached a whole new level. Honestly, there's not too much to say here other than, "Told you so."

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Wednesday, October 25, 2006

Ah, medical marijuana

Taken from www.counterpunch.org :

It has been 10 years since California voters enacted Proposition 215, making it legal to grow and use cannabis, with a doctor's approval, for medical purposes. Prop 215 didn't create a record-keeping system because the authors didn't trust the government and didn't want to generate a master list of cannabis users. So, over the course of the past decade, a vast public health experiment has been conducted in California but no state agency has been tracking doctors who approve cannabis use or patients who medicate with it.

To assess the results in the absence of government-garnered data, I surveyed doctors associated with the Society of Cannabis Clinicians. The SCC was founded by Tod Mikuriya, MD, in 2000 so that doctors monitoring their patients' use of cannabis could share data for research purposes (and, alas, respond to threats from federal and state authorities). More than 20 doctors have attended SCC meetings, which are held quarterly. Philip A. Denney, MD, is the current president.

Some responses to the survey have not yet been received, but it appears that the specialists have approved cannabis use by more than 140,000 patients. "Approve," not "recommend," is the apt term, since more than 95 percent of the patients consulting specialists had been self-medicating previously.

The specialists account for approximately 40% of the letters of authorization on file with an agency that issues ID cards on behalf of cannabis dispensaries (to spare them having to confirm the validity of each customer's letter of approval). Extrapolating from this ratio, I estimate the number of Californians who have used and/or provided medicinal cannabis legally under Prop 215 to be about 350,000.

The complete survey will appear in the Fall issue of O'Shaughnessy's, a journal I produce for the SCC. What follows are excerpts from the response of Jeffrey Hergenrather, MD, a former family practitioner who has been conducting cannabis consultations in Sebastopol since 1999.

Q. How many patients will have received your approval to use cannabis through October 2006?

A. 1,430

Q. What percentage had been self-medicating with cannabis prior to consulting you?

A. 99%

Q. With what medical conditions have they presented? List top five and approximate percentage (total can exceed 100%).

Chronic pain (62%), Depression and other mental disorders (30%), Intestinal disorders (12%), Harmful dependence (10%), Migraine (9%) are the most common conditions being treated.

Q. What results do patients report? How does cannabis appear to work in treating their symptoms?

A cannabis specialist soon becomes aware of two remarkable facts. The range of conditions that patients are treating successfully with cannabis is extremely wide; and patients get relief with the use of cannabis that they cannot achieve with any other pharmaceuticals.

The testimonies that I hear on a daily basis from people with serious medical conditions are moving and illuminating. From many people with cancer and AIDS come reports that cannabis has saved their lives by giving them an appetite, the ability to keep down their medications, and mental ease. No other drug works like cannabis to reduce or eliminate pain without significant adverse effects. It evidently works on parts of the brain involving short-term memory and pain centers, enabling the patient to stop dwelling on pain. Cannabis helps with muscle relaxation, and it has an anti-inflammatory action. Patients with rheumatoid arthritis stabilize with fewer and less destructive flare-ups with the regular use of cannabis.

Other rheumatic diseases similarly show remissions. Spasticity cannot be treated any more quickly or efficiently than with cannabis, and, again, without significant adverse effects.

Patients who suffer from migraines can reduce or omit conventional medications as their headaches become less frequent and less severe.

About half of the patients with mood disorders find that they are adequately treated with cannabis alone while others reduce their need for other pharmaceuticals. In my opinion, there is no better drug for the treatment of anxiety disorders, brain trauma and post concussion syndrome, ADD and ADHD, obsessive compulsive disorder, and post-traumatic stress disorder. Patients with Crohn's disease and ulcerative colitis are stabilized, usually with comfort and weight gain, while most are able to avoid use of steroids and other potent immunomodulator drugs.

People who were formerly dependent on alcohol, opiates, amphetamines and other addictive drugs have had their lives changed when substituting with cannabis. Patients with end-stage renal disease on dialysis and those with transplanted kidneys show mental ease, comfort, and lack of significant graft-versus-host incompatibility reactions in my small series.

Diabetics report slightly lower and easier-to-control blood sugar levels, yet to be studied and explained.

Sleep patterns are typically improved, with longer and deeper sleep without any hangover or significant adverse effects.

Many patients with multiple sclerosis report that their condition has not worsened for many years while they have been using cannabis regularly. MS and other neurodegenerative diseases share the common benefits of reduced pain and muscle spasms, improved appetite, improved mood and fewer incontinence problems. Many patients with epilepsy are adequately treated with or without the use of other anticonvulsants.

Patients with skin conditions associated with systemic disease such as psoriasis, lupus, dermatitis herpetiformis, and eczema all report easement and less itching when using cannabis regularly.

Airway diseases such as asthma, sleep apnea, COPD, and chronic sinusitis deserve special mention because I encourage the use of cannabis vapor or ingested forms rather than smoking to reduce airway irritation. Finally, most obese and morbidly obese patients respond with weight loss and improved self esteem. I believe that cannabis and psychotherapy work well together in fostering behavioral changes.

Q. Have you compiled demographic data or can you estimate the breakdown with respect to your patients' age, gender, race, economic status?

Gender: 62% male, 38% female. Ages range from 14 to 86 years old. The male mean age is 45.9 years with a median age of 46. The female mean age is 47.4 with a median age of 48 years. The graphs of the age and gender distribution are similar with the exception that there is a bump in the leading edge of my male patient population as compared to the females, which I account for by young men's work injuries, sports injuries, motor vehicle accidents, and problems stemming from military service, including injuries and post-traumatic stress disorder. The vast majority of patients in my practice are of Caucasian / Indo-European descent, with only about 1% African-American, 2% Native American, 1% Pacific Islanders, and 2% Asian.

Q. Have you observed or had reports of adverse effects from cannabis? If so, please describe.

Is there a downside to the use of cannabis? The sense of intoxication rarely lasts longer than an hour and tends to be more troubling to the novice than to the experienced user. For some people cannabis can induce dry mouth, red eyes, unsteady gait, mild in-coordination, and short-term memory loss, all of which are transient. These effects are reportedly trivial compared to those brought on by pharmaceutical alternatives.

Cannabis use is steadily finding acceptance in society. Still, for many it remains awkward if not totally impractical in the workplace. People whose jobs require multi-tasking such as pilots, drivers, dispatchers, switchboard operators, and many professionals find the intoxicating effects of cannabis inappropriate in the workplace, and therefore reserve their use for after work. Strains

Q. What have you learned re strains and dosage?

Cannabis is a complex, un-patentable plant with vast pharmacologic potential. Different strains contain different mixes of cannabinoids and terpenes that give them distinct qualities. Some strains energize you; others put you to sleep. Many patients, when they find a strain that suits their needs, try to obtain it on a regular basis. Unless they are growing their own from cuttings, however, they have to rely on growers and distributors to reproduce and make available the preferred strain from year to year.

Due to Prohibition, California growers have been denied the tools of analytical chemistry to test the cannabinoid contents of their plants. This has impeded the development of strains aimed at treating various conditions. Nevertheless, patients continue to educate themselves about cannabis as medicine and how best to use it. Over the years that I have specialized in cannabis therapeutics, health benefits reported by patients have been substantiated and explained by findings from research centers around the world.


And marijuana is illegal....why? Oh, yes, that's right, because of a racist and hypocritical drug war that's fueled by politics and greed. Good show, America!

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Marijuana and my world

Marijuana is a unique plant - this much can not be disputed. What other plant is like it? What other plant has so many medicinal uses? What other plant has unique, visible sexes? What other plant can be used so widely in industry? What other plant can bring about spiritual, philosophical, and otherwise higher thinking revelations? What other plant can make you so relaxed? What other plant can enhance everything, make everything look, taste, feel, smell, and sound better? What other plant is so harmless that it not only will it not give you cancer if smoked, but will even prevent it? What other plant can make everything so fresh and new that even the simplest of "inherent" cultural values become the most obscene picture of absurdity ever painted by so-called intelligence?

Indeed, what other plant possess all these qualities? There is no doubt that there are separate plants that could meet most of the qualities of marijuana - psilocybe mushrooms can do many, for example. None, however, contains all of these at once. What kind of strange plant is this? What is its purpose, this plant that grows so fervently and spreads with such zeal that it has been dubbed "weed"? Is it even native to this planet we call home and Earth?

Could it be, perhaps, that marijuana is a complex plant meant to treat a complex problem? For those of you that have any experience with Terrence McKenna and his thoughts on psychedelics, this may sound familiar. Indeed, marijuana is a psychedelic, although not to the magnitude of most psychedelics. It will not produce a trip like psilocybe mushrooms or the peyote cactus or the ayahuasca brew, no, but neither do those psychedelics have the physical healing capacities and industrial uses of cannabis. Marijuana is not especially strong in any one field, indeed it is often thought of as being able to compliment most other psychoactives. What drug is out there that does not go great with cannabis? Scary, terror-filled drugs that are more poison than anything else, and even then one may find marijuana comforting.

Erowid lists cannabis as a, "stimulant, depressant, psychedelic" and as an "intoxicant." It can be all of these things and it can be none of this these things. It can be some of these things, a combination of these things, or a combination of the subsets of these things. Marijuana, in a way, is a metaphor for life. It is the infinity: all energy and life are merely derivatives and subsets within the infinity, all possibilities are traveled and chaos produces the creativity and originality that turns the universal infinite consciousness from a deterministic experiment to the playground of energy. Truly, what else could one call life? It is the playground of energy, of motion, of vibrations and waves, of ups and downs, male and females, good and evil, the bottom and the top of the wave. In the center is the balance, the asexual, the absolute zero, and also the infinity. Infinity is special like that - where it exists, it exists everywhere, for that is its nature. This may seem obvious, but to state something and to actually be able to perceive it are two different things. Can you truly perceive the infinite?

I can, to a degree. I would not be able to do it without cannabis - at least not in the way I am describing. The eyes I see through are the eyes of energy, of chaos, and of love - but at the same time I see through the eyes of complete stillness, of perfect order, and of destructive asymetry. These conflicts rage against each other in only a manner in which waves can battle and copulate, with each further hit taking the next to an exponentially smaller infinity. Indeed, that is what I am doing with marijuana: with each further hit I am becoming exponentially closer to the smallest infinity.

Many people who are spiritual view a higher conciousness as, well, "higher", moving UP, like steps on a pyramid. This highlights a central flaw in the way the whole basic idea is trying to be symbolized: the highest conciousness of infinity is no movement at all - absolute zero. In other words, infinity is also known as nothing - it doesn't exist, but it does in a way in which it is extremely hard to wrap the physical mind around. When one reacts, you are displacing energy and creating more waves and vibrations - moving further away from the absolute. I have to give credit where credit is due - Ate introduced me to this idea: allowing energy (life, chaos, vibrations, etc) to flow around you and not reacting, you gain greater control. The smaller the wave, the more control you have over it. However, one must recognize that duality is present in every situation, especially those regarding duality itself (moderation in moderation). When one achieves total control over everything, you realize that total control is no control at all. The more you try and control something, the less you actually do. The more you just let things be, the more you are letting them be, and thus you are controlling them by optimizing their inherent purpose.

This is the world I see with cannabis, this is the universe that it has shown me, that it takes me to with every inhalation to every exhalation. I am the alpha, and marijuana is the omega. Yahweh - God - His name literally means, "I am what I am" , or in more simple terms, "I am". That is the infinite consciousness, the absolute, the zero, the ultimate vibration of no vibration of all. The only eternal truth, that which is, is, or mathematically, 1 = 1. Descartes famously said, "I think, therefore I am," I would like to point out that if a = b, then b = a, as well. I think = A, I am = B. Not only is it true that all things that are, think, all things that are, think. Yes, that's right, all things are part of the infinite consciousness - that's what infinity is, everything. You are part of it, so show yourself some love, treat everything with respect, and learn true unity. Anything that is matter is energy, and anything that is energy is life - and should be treated with love. Yes, even a rock should be treated with love. Why shouldn't it? Just because it doesn't meet our perceptions of what life is?

Marijuana is alive, and in more ways than one. You would not regard your wise grandpa as a tool, even though he has a purpose to you, would you? If you did, you would be thinking in cold, logical terms that eventually end up contradicting themselves as they are not aligned with the infinite truth. Marijuana is not a tool, although it serves many purposes, marijuana is a companion, another living being with a soul and a purpose and an existence. Every time you strike a flame to it, remember that, and treat it with the respect it deserves, and it will treat you with the respect you deserve and have shown.

I have no more panic attacks while high. I have no anxiety, no paranoia, no bad vibes, bad thoughts, bad feelings, or otherwise. And yes, I get very fucking high. I treat marijuana with love and respect and in return it does the same; it dissolves boundaries and I impart patterns. True patterns are not those that define a set to a limit - true patterns know that there are no limits. With each hit, more boundaries are dropped and less limits are set, more skies are opened. When you have the infinite, anything is possible. When you are the infinite, you are possible. When you stop being high and begin to be high - that is, to be the high, when you for a give-give, love-love relationship, the plant becomes part of you. You return to each other as all things are.

This sounds absurd, but at the core of all absurdity is truth. There are some plants that we share more DNA with than with other animals - why would it be hard to think marijuana is an extension of our souls? No, I take that back, they are not extension, they are our souls, as all things are, as I am you and you are me. I am what I am, you are what I am, and I am what you are. We are the alpha, we are the omega.

I am the up. I am the down. I am the balance, I am the derivative. I am all the shades of grey, all the rainbows and all the fractals. I am every wavelength there is, I exist on all planes and in all dimensions. I live in every place and in every time, in every universe and in every atom.

Marijuana is my world.

Love.

-R

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Monday, October 9, 2006

Rizzo the mythbuster: Snorting benzos DOES work

In this post, I will not only conclusively show that administering benzodiazepines such as diazepam, lorazepam, and alprazoram work, but also work effectively.

It is a common perception among people who consider themselves knowledgeable about drugs that benzodiazepines such as diazepam can not be taken intranasal. The idea is that since benzos are not water soluble, they can not be absorbed in the mucous membranes in the nose, and thus only the drip (see: phlegm, a water based gel substance) gets you high, when it eventually reaches your stomach. This perception is fairly widespread, and so-called "n00bs" are lambasted for snorting any type of benzo outside of midazolam, a water soluble benzo. Considering there has been no scientific proof brought forth that to take benzos intranasal they have to be water soluble, I think it is safe to say for many people this is a matter of ego. Since there has been no scientific proof linking water solubility to benzo inefficiently in the nasal mucosa, I would like to point out that this should not be considered the de facto truth.

First of all, absorption of drugs commonly takes place in one of the many mucous membranes in the body. These places include the nose, the anus, the lips, under the tongue, the ears, and the genital area. (Wikipedia article on mucous membranes.) Drugs (among other things) are absorbed through the mucous membranes, into the local veins, into a main artery, and then soon after are to the brain. The advantage of taking drugs this way is that it bypasses first pass metabolism of the liver, which is extremely destructive to drugs, and it reaches the brain much quicker. This is why intranasal, sublingual, and anal administration is usually preferred to oral.

Bioavailability is a term used to describe the fraction of a dose that reaches the systemic circulation, or in more basic terms, how much of drug X that is actually reaching your brain. It is a basic description for determining how effective a certain method of administration is. One of the most important of these is lipid solubility. Lipids are a group of naturally occurring organic compounds that are related by their solubility in nonpolar organic solvents, and generally their insolubility in water. Although bioavailability also depends on a number of other factors, including but not limited to pH, molecular weight, etc, lipid solubility is the most important and the one I will be focusing on. Molecular weight does not matter that much seeing as how cocaine is a substance taken intranasal with a molecular weight of 303.353 g/mol, and diazepam has a molecular weight of 284.7 g/mol. The pH of a substance can be modified through different methods, and thus is not that important.

The intranasal bioavailability of diazepam in dogs is a whopping 80%, according to this study which states:

Mean bioavailability of BDZ following IN administration was 80 +/- 9%. CONCLUSIONS AND CLINICAL RELEVANCE: Diazepam is rapidly and efficiently absorbed following IN administration of the parenteral formulation. Plasma concentrations match or exceed the suggested therapeutic concentration (300 microg/L). Intranasal administration of diazepam may be useful for treatment of seizures in dogs by owners or when intravenous access is not readily available.

Obviously dogs are different than humans, but the nasal mucous membranes of mammals does not differ that much. Taken alone, this bit of information might not be conclusive, but there is more:

The purpose of this study was to evaluate the pharmacokinetic profile of intranasal lorazepam in comparison to currently established administration routes. Eleven healthy volunteers completed this randomized crossover study. On three occasions, each separated by a 1-week washout, subjects received a 2 mg dose of lorazepam via the intranasal, intravenous, or intramuscular route. Blood samples were collected serially from 0 to 36 hours. Noncompartmental methods were used to determine pharmacokinetic parameters. Lorazepam was well absorbed following intranasal administration with a mean (%CV) bioavailability of 77.7(11.1). Intranasal administration resulted in a faster absorption rate than intramuscular administration. Elimination profiles were comparable between all three routes. The concentration-time profile for intranasal delivery demonstrated evidence of a double peak in several subjects, suggesting partial oral absorption. Females were found to have significantly higher AUC values than males for all three delivery routes. Overall, this study demonstrated favorable pharmacokinetics of intranasal lorazepam in relation to standard administration methods. Intranasal delivery could provide an alternative, noninvasive delivery route for lorazepam.

Taken from this study. Not only is intranasal administration an efficient method, but my personal favorite method, sublingual, is also efficient:

Ten healthy volunteers received single 2-mg doses of lorazepam on five occasions in random sequence. Modes of administration were: A, intravenous injection; B, deltoid intramuscular injection; C, oral tablets in the fasting state; D, sublingual dosage of oral tablets in the fasting state; and E, sublingual dosage of specially formulated tablets in the fasting state. Kinetic variables were determined from multiple plasma lorazepam concentrations measured during 48 hr postdose. After intravenous lorazepam, mean (+/- SE) values were: elimination half-life (t 1/2 beta), 12.9 (+/- 0.8) hr; volume of distribution, 1.3 (+/- 0.07) liters/kg; total clearance, 1.21 (+/- 0.1) ml/min/kg. Absorption of intramuscular lorazepam was rapid. Peak plasma levels were reached at 1.15 hr after dosage, with absorption half-life averaging 14.2 (+/- 4.7) min. Absorption or oral and sublingual lorazepam tended to be less rapid than intramuscular injection, although differences were not significant. Times of peak concentration were 2.37, 2.35, and 2.25 hr postdose for trials C,D, and E, respectively; values of absorption half-life were 32.5, 28.5, and 28.7 min. Absolute systemic availability for trials B, C, D, and E averaged 95.9, 99.8, 94.1, and 98.2%, respectively; none of these differed significantly from 100%. Values of t1/2 beta were highly replicable within individuals regardless of the administration route. Thus, sublingual lorazepam is completely absorbed and is a suitable administration route in clinical practice.

From here. Here are some more studies that further prove my point:

Intranasal lorazepam is effective, safe, and provides a less invasive alternative to intramuscular paraldehyde in children with protracted convulsions. The ease of use of this drug makes it an attractive and preferable pre-hospital treatment option.

http://tinyurl.com/or2zo

Intranasal benzodiazepines produce rapid and effective sedation in canaries. Intranasal alpha(2) agonists produce sedation but not sustained recumbency. Specific antagonists are also effective when used by this route. Clinical relevance Intranasal sedative drug administration is an acceptable alternative method of drug delivery in canaries.

http://tinyurl.com/o56df

Not only is intranasal administration of benzodiazepines an efficient method in the medical community, it has been shown that it is widespread in the drug (ab)using community:

Two cases of intranasal benzodiazepine use are presented. The methods of preparation and administration of the powder and accounts of the pharmacological effects of the drugs used are described. The pattern of development and progress of the habit and its associated features are delineated. Snorting benzodiazepines appears to be more common than is currently appreciated, and the clinical complications and implications of this habit are discussed.
http://tinyurl.com/qtfaf

In conclusion, intranasal administration of benzodiazepines is not only an extremely efficient method of use, but is also prevalent in the recreational drug community. I have shown that drug absorption in the mucous membranes relies on lipid solubility, not water solubility, and that drugs that are lipid soluble are very often water insoluble. There is no scientific evidence whatsoever to give the impression that water-insoluble benzodiazepines can not be taken intranasal, and thus it is a 100% positive fact that it is a myth. Water insoluble benzos can be snorted, are snorted, and if one so desires, should be snorted.

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