Providing straightforward information pertaining to drugs, drug use & drug policy. The Grey Pages promotes drug-related literacy and advocates a system of viable and tolerant drug policies. This is my personal collection of commentaries, essays, tid-bits, and other such writings on everything ranging from drug use, drug policy and drug-myths, to drug-science, addiction, human behavior, and the workings of the human brain. I started this blog with a particular focus on opioids, and over the past year have found my interest gravitate toward the intriguing, ever-changing world of designer intoxicants (i.e. "research chemicals" or "designer drugs").

Wednesday, December 22, 2010

Oxycodone Images Page

Oxycodone IR 15mg tablets

Oxycodone IR - 30mg tablets

The updated bottle and labeling for OxyCont

2 different dosages of OxyContin

OxyContin 80mg tablets;
Oxycodone IR 30mg tablets

Several dosage strengths of the newer
formulation OxyContin (OP Tablets)

Vial of OxyNorm, an oxycodone injectable solution;
Oxycodone 5mg capsules
Endocet - A combinaton of oxycodone and acetaminophen

Sunday, December 19, 2010

Pain Pt. 2: Spinal Sensitization and Neuronal Excitability

The process of "pain", step by step, is as follows:

1) Painful Stimuli is sensed in skin or muscle tissue, by a sensory pain receptor.

2) The signal is transmitted from the affected area in the periphery, traveling up the spinal cord through sensory fibers (delta A and C fibers) which are located mainly in the superficial layers of the dorsal (posterior) area of the spinal cord and intersecting at the substantia gelatinosa and the nucleus proprius, to synapse pathways of the spinothalamic tract.

As described in a previous entry (see 'pain perception' entry) two key 'pain' neurotransmitters are glutamate and substance P. - both work synaptically (between nerve endings) to carry signals from one nerve (A and C pain fibers) to the next (spinothalamic tract).

3) At this point, once relayed from A and C fibers to the next pathway, signals travel up the spinothalamic tract to connect with the thalamus.

4) Signals continue from the spinothalamic tract and the thalumus, to areas such as the cingulate cortex, somatosensory cortex, the periaqueductal grey area, and various limbic structures.

Certain medications such as NMDA receptor antagonists work by blocking (or antagonizing) glutamate receptors; heavily within the spinal cord dorsal area. These agents include ketamine, PCP, and dextromethorphan. Other medications which work differently but have additional activity as NMDA antagonists are the opioid agonists methadone and levorphanol. Anti epileptic medications such as gabapentin and pregabalin work by inhibiting the release of glutamate from peripheral nerve endings in the spinal cord.

Inbound pain signalling to the brain is additionally affected (inhibited or enhanced) by descending signals originating from the brain (PAG). SSRI or Tricyclic antidepressant medications including amitriptyline and duloxetine may reduce pain by increasing the inhibitory affect of this descending pathway on ascending pain stimuli.

The amount of pain felt by an individual is not experienced on a linear level with the degree of pain stimuli; i.e what may be experienced as little to no pain for one person, may be experienced as severe or debilitating pain for another.

Chronic periods of pain from the periphery (peripheral nervous system) such as that experienced with arthritis, spinal stenosis, musculoskeletal injury and rheumatic degenerative conditions is likely to lead to increased central sensitivity - the descending pain modulatory system adapts to long term pain. To put simply, during long periods of pain transmission up the spinal cord, it is able to memorize and perpetuate this state, through positive feedback, leading to excessive pain-flow, even in the absence of any actual injury or illness.

A large part of pain sensitivity is modulated by the transmission of glutamate and substance P, at synaptic sites throughout the spinal cord. There are multiple points between the sensory receptor (origin of the signal) and the brain (interpretation of the signal) that a signal may be amplified by increased neuronal excitability and excess release of glutamate/substance P.

In addition, sensory (pain) receptors have their own individual threshhold; where any stimuli exceeding this threshhold will trigger the receptor to send a pain signal - Some individuals will have a lower threshhold for these receptors than others.

Those with fibromyalgia for instance, typically experience spinal (or central) sensitization through both of these phenomena - increased neuronal excitability and low threshhold for pain stimuli. 

The latter often manifests in an increased tenderness to a given pressure; which is the origin of the 'tender point test' which serves as a diagnostic tool for the condition of fibromyalgia.

Saturday, December 11, 2010

Resistant Cases of Depression and the Medicalization of the Human Condition

The monoamine based classes of modern day antidepressants include some of the most widely over used and over rated agents for treatment of depressive and anxiety disorders. This broad class of psychoactive drugs includes:
  • Selective Serotonin Reuptake Inhibitors (SSRI drugs)
  • Monoamine Oxidase Inhibitors (MAOI drugs)
  • Tricyclics (TCA drugs, or tricyclic antidepressants)
The tricyclic class of antidepressants were the originally used 'gold standard' in depression pharmacotherapy, but come with a range of bothersome side effects (not to mention toxic concerns). The MAO class works through a slightly different mechanism than the SSRI class to achieve the same goal of increasing synaptic serotonin levels; but come with extreme diet restrictions and a dangerously high likelihood of adverse interactions (with other substances). The MAO inhibitors, unlike SSRI drugs, are highly unselective. For these reasons, SSRI drugs are perhaps the most commonly used by psychiatrists, internists, and family practitioners in treating mood and impulse disorders.

Those with a history of occasional or regular opioid use present a challenge in terms of succesfully treating depression and anxiety. Much of the opioid user population is predisposed to mood disorders, and in effect either consciously or sub-consciously self medicate with opioids. Severe depression, anxiety and panic disorder, OCD, and suicide attempts are common and likely in this population. It is no coincidence that severely distressed beings are drawn to this class of chemicals, and also no coincidence that the opioids, temporarily, alleviate symptoms of severe depression and anxiety; mu and delta opioid activity mediate an increase in dopaminergic activity - a trait which opioids share with certain drugs of the antidepressant class:

Now looking at it the other way, SSRI class drugs used in treating depression have been shown to have positive effects on endogenous opioid peptide production (production of natural chemicals in the body which block pain and suffering - the bodies natural opioids)

In addition, opioids work by decreasing neuronal excitability - this is achieved in part through their inhibitory effect on the Locus Coeruleus. This specific function plays a primary role in their anxiolytic (anti anxiety), stress reducing properties.

I believe that the specific targeting of serotonin in the treatment of severe depression does little to effectively eliminate symptoms; this may be evidenced by the very modest (low) response rates of most SSRI and MAOI drugs; especially when you contrast this low response with the much better response of dopaminergic agents - which may include psychostimulant drugs such as methylphenidate and dextroamphetamine, as well as slower acting, less selective/specific drugs such as bupropion and modafinil.

It may be important to mention the drug Sertraline, of the SSRI class. Sertraline is unique among its class in that it shows significant affinity for the dopamine transporter; acting as a dopamine reuptake inhibitor in addition to its effects on serotonin. Sertraline (known by the brand name Zoloft) I believe may be somewhat effective in treating cases of severe depression in the opiate addict population - in fact, this could extend to apply to a large population of comorbid addictive/depressive cases.

In addition to Sertraline: Bupropion (Wellbutrin), Venlafaxine (Effexor), Modafinil (Provigil), and Tramadol (Ultram) have unique properties which will likely suit them for the treatment of comorbid addictive/depressive cases.

As discussed in earlier blog entries, dopamine plays a crucial role in the mechanism underlying true addiction and compulsive behaviors; which include drinking, gambling, anorexia, drug use, shoplifting and hoarding.

On a final note: Let me make it clear that I do not support the progressive 'medicalization' of any and all human behaviors which differ from the norm; I believe the brain chemistry and personality traits of every individual are unique in all cases, and when looking at the brain 'under a microscope' so to speak; there will always BE a patho-neurological/biological mechanism behind each and every human behavior - 'Different', even when explained pathologically, does not constitute a clinical diagnosis of an 'illness' or disorder... At least not in every case. A new 'illness' will be invented every so often; I believe, eventually to the point where there is not a single man woman or child in the world who is not diagnosed with some obscure list of ailments.

Friday, December 10, 2010

First New Analgesic Compound In 25 Years - Nucynta (Tapentadol)

Tapentadol: This is the first centrally acting analgesic (pain reliever) of its type to be released to the market in over 25 years. Chemically, tapentadol is closely related to the weaker drug, tramadol. It was in fact synthesized to emulate the properties of tramadol's highly active metabolite known as M1, or O-Desmethyltramadol - the main metabolite of tramadol, having roughly 200x stronger binding affinity for the mu opioid receptor.

Tapentadol works through two mechanisms; acting as a norepinephrine reuptake inhibitor (or NRI) and as a mu opioid receptor agonist. Drugs of the norepinephrine reuptake inhibitor class are commonly used as secondary analgesics to supplement opioids, and additionally for treating depressive and anxiety spectrum disorders. A norepinephrine reuptake inhibitor can be expected to have stimulating 'upper'-like qualities; drugs of the amphetamine class act on norepinephrine.

Together, the combination of NRI as well as opioid activity can be expected to provide better pain relief than either of the two alone. Tapentadol provides a dual mode of action in a single compound.

The potency of this drug falls into the mid-range of narcotics, similar to oxycodone and hydrocodone. Milligram for milligram, tapentadol is less potent than these drugs, therefore the drug is manufactured in strengths of 50mg, 75mg, and 100mg tablets. Opiate users and addicts report desired pleasant effects and euphoria to become apparent in the higher dose range of 200mg to 300mg however this will vary based on individual tolerance to opioids.

Some have reported the overall effects to be similar to those of oxycodone. Relief of pain, euphoria, chattiness and sociability, empathy, increased energy, miosis, constipation and possible respiratory depression in high doses are all likely effects a lesser degree of sedation relative to other narcotics and likely stimulant effects are to be expected.

Nucynta is available in the three dosages pictured below: 50mg, 75mg, and 100mg.

Thursday, December 9, 2010

Atypical Analgesics



Tapentadol is a centrally acting analgesic with a dual mode of action as a norepinephrine reuptake inhibitor (NRI) and a selective mu-opioid agonist. The dual mode of action distinguishes it from other opioids. Tapentadol is very young to the US market as it was released within the past 3 years.


Nucynta: 75mg Tablets (Tapentadol HCL)
Tapentadol (brand name Nucynta) is used to treat moderate to severe acute pain. Currently the drug is solely available in the short acting form, which suit it for acute or short term pain. Its dual mode of action suits it for atypical types of pain which may show little or no response to conventional analgesics such as typical narcotics or NSAID's/APAP. Nucynta is most often useful for acute, irregular pain such sprains, fractures, lacerations, burns, toothache, headache or postoperative pain. It may also be used (as it increasingly is) in chronic pain therapy as a supplemental analgesic for episodes of sudden onset or breakthrough pain - typically in patients being treated with a traditional long acting narcotic such as morphine, oxycodone, or transdermal fentanyl. In a marketing and clinical sense; It plays a role similar to that of Dilaudid, if merely in the sense that its rapid acting/short-lived properties lend an 'acute or breakthrough' treatment appeal to the drug.

Based on clinical evidence and literature, it is suggested that tapentadol in the dose range of 50 to 100mg produces analgesia comparable to that of a 7.5 to 15mg dose range of oxycodone IR.

Tapentadol is currently under patent and as such is available only as the original brand name product, Nucynta - the name being derived from "New", and "Synthetic" - as it is the first centrally acting analgesic (not to mention opioid) to be marketed in the US within the last 25 years. Nucynta is currently available as tablets for oral use, in doses of 50, 75, and 100 milligrams.


Chemically, tapentadol is a novel analgesic acting as a functional analogue to a major metabolite of tramadol. Technically, atypical analgesics such as tapentadol (or tramadol) show superior potential in treating a spectrum of depressive-anxiety or personality disorders; due to a dual mode of action - i.e. monoaminergic agent (SRI, NRI) and opioid agonist. The latter offers a profound boost in efficacy - especially appealling to the mainstream when combined with the serotonin/norepinephrine properties. Tapentadol is pharmacologically similar to tramadol and o-desmethyltramadol ("M-1"), but has a greater affinity & efficacy at mu-opioid receptors, and a correspondingly greater dependence-tolerance liability.

Tapentadol is 18x less potent than morphine as a mu agonist. Tapentadol is 2-3x less potent as an analgesic according to animal-studies. This is supportive of its multiple modes of action (NRI + mu-agonist)

Molecular Structures of tapentadol

Tapentadol is centrally active in itself - pharmacological effects of the drug are produced by tapentadol rather than a metabolite. Tapentadol was created as a structural/functional analogue of tramadol's major active metabolite o-desmethyltramadol and was succesful in emulating these pharmacological properties. Tapentadol shows a high affinity and selectivity to the mu-opioid receptor, with a clinically negligible affinity for kappa & delta receptor. Additionally, the drug acts as an inhibitor of norepinephrine reuptake (NRI) as well as a modest inhibitor of serotonin reuptake (SRI) - Studies showed tapentadol to produce dose dependent increases in extracellular norepinephrine levels up to 4x greater than baseline, with serotonin levels showing a modest dose-wise increase of up to 30% higher than baseline. This second mode of action as an (S)NRI compensates the relatively mild mu-opioid properties by creating a pharmacological synergy which produces greater analgesia than either mode of action alone.

Bioavailability after oral administration is approximately 32% owing to extensive first pass metabolism. The drug has a half life of approximately 4 hours. Excretion/elimination of tapentadol is almost completely via the kidneys (renal).


According to an abuse liability study sponsored by the manufacturer, the minimum available dose of 50mg tapentadol produced subjectively similar opioid effects (euphoria, anxiolysis) to that of 4mg of oral administered hydromorphone. The study went further to suggest that tapentadol in doses of 100mg and 200mg produced similar subjective narcotic effects to hydromorphone doses of 8mg and 16mg respectively.

Those who have used the drug therapeutically or recreationally have reported common side effects; including the usual spectrum of opioid side effects (itching, miosis, emesis, respiratory depression) in addition to stimulant type side effects (hypertension, restlessness, jittering, anxiety, tension, insomnia)

Tapentadol in opioid tolerant individuals may not produce significant narcosis at therapeutic doses, however those who have attempted higher doses (400-600mg) describe effects as quite pleasant, similar in nature to oxycodone; i.e. euphoria, anxiolysis, positive mood.



Tramadol is a bicyclic (2-ring) synthetic analogue of codeine
Tramadol is a synthetic non opium based compound created as a structural analogue of codeine with multimodal activity (note the similarity in structure on the left). The drug is available for oral use as a single entity product by the brand name Ultram; as a compound with acetaminophen by the brand name Ultracet; or as a solution for parenteral use. Tramadol as a branded drug is marketed by its creator Grunenthal, a german pharmaceutical firm.

Tramadol is a centrally acting analgesic with opioid and non opioid activity; used in the US and elsewhere for the treatment of moderate to moderately severe acute or chronic pain.

Tramadol is pharmacologically related to tapentadol, i.e. Nucynta. And structurally related to the popular antidepressant drug venlafaxine, known by its brand name Effexor, or the newer stereospecific product, Pristiq.


Despite only mild opioid action, tramadol is effective as an analgesic, and is reported to be euphoric by some opiate naive users. Its use in medicine is relief of mild to moderately severe pain. If tramadol is the only option available, it might very well be effective in cases of severe pain, most likely in those not already taking narcotics for pain. Tramadol is usually given for acute pain such as that associated with urgent care or ER visits. Ultram is often given by doctors to suspected "drug-seekers" in either of the aforementioned settings. It may be used for dental pain such as a simple toothache, or after minor procedures such as fillings, root canal, or tooth removal. Tramadol is a good choice for burn or laceration pain, and for the pain of a severe tension headache or migraine. Tramadol has been given long term for fibromyalgia, diabetic neuropathy, and other cases of neurological pain, usually taken 'as needed' - for pain flare-ups. A long acting tablet form of tramadol is currently available as Ultram ER, offering analgesia aound the clock.

Tramadol has been used off label to treat symptoms of major depressive or anxiety disorders, usually after various tireless courses of the more toxic but morally acceptable tricyclics, SSRI's & SNRI's, MAOI's, benzodiazepines and perhaps amphetamines have failed. Its particular efficacy for depression and anxiety derives from the addition of opioid activity as a complement to the serotonin-norepinephrine enhancing properties. The opioid component provides unquestionable efficacy as an antidepressant, with a lesser level of dependence than a full agonist, even codeine. The opioid component also provides greater anxiolysis than an SSRI without the cognitive or psychomotor impairment seen with long term benzodiazepine use, and may smooth out some dirty or lethargic side effects of the monoaminergic activity.


Tramadol is a racemic compound composed of a (1R, 2R) enantiomer and a (1S, 2S) enantiomer. The (R) enantiomer is responsible for the opioid and serotonergic effects while the (S) enantiomer is responsible for the noradrenergic effects.

Tramadol has a dual mode of action acting as a weak opioid agonist and a serotonin-norepinephrine reuptake inhibitor. The drug is highly selective at the mu opioid receptor but with a weak efficacy - meaning it produces a weak agonist effect. Some literature classifies tramadol as a partial opioid agonist. Though the parent drug itself contributes to the SNRI effects of the drug, tramadol relies on its more potent O-demethylated metabolite, O-desmethyltramadol (or M1), for most of its mu opioid analgesic activity. M1 is believed to be 6x more potent of an analgesic than tramadol, with roughly 200x tramadol's affinity for the mu receptor, and additional activity at the norepinephrine transporter. To summarize its pharmacodynamic profile; The SRI efficacy is produced by tramadol itself; while the NRI activity is produced by both tramadol and O-desmethyltramadol.

The multimodal action of tramadol and similar drugs derives its efficacy from the synergistic action between the opioid system and the serotonergic and noradrenergic systems. While mu receptors stem the flow of pain to the brain and changes the experience of pain; serotonin and to some extent norepinephrine modulate spinal pain modulation pathways which run from the brain to the dorsal horn; stimulating the endogenous opioid system and further stemming pain flow to the brain. Tramadol induced analgesia is only partially antagonized by naloxone, supporting the notion that the SNRI actions contribute to its efficacy. Current research continues to identify previously unknown connections between the serotonergic/noradrenergic and the opioid system. This could raise many more questions pertaining to a role of the opioid systems in modulation of anxiety or depressive disorders.

Tramadol is well absorbed orally with a bioavailability of 75%. Tramadol is metabolized by the liver, undergoing N and O-demethylation, sulfation, and glucuronidation. O-demethylation carried out by CYP2D6 forms its active M1 metabolite - making it susceptible to drug interactions or a lack of response in those who lack the 2D6 enzyme (i.e. about 7% of the population). Those who are non responsive to codeine may be non responsive to tramadol. Tramadol is additionally a substrate of CYP3A4. The parent drug and its metabolites undergo second phase conjugation, and are excreted renally - i.e. mainly through the urine.

Tramadol begins to produce effects one hour after dosing, which reach a peak at 2 to 3 hours. Tramadol itself has an elimination half life of 6.3 hours, M1 has a half life of 7.4 hours. As such, tramadol is longer acting than codeine, hydrocodone, and other opiates, with efects which may last up to 8 hours. Tramadol is typically given every 4 to 6 hours when prescribed for pain. Steady state blood levels are generally reached within 2 days with regular dosing (every 6 hours).


Being a mild opioid, tramadol produces some subjective effects and side effects that are similar to opioids such as codeine. Although these effects may be less pronounced, or unattainable in the opioid tolerant individual.

Subjective effects may include analgesia, anxiolysis, wakefulness or trouble sleeping, a sense of motivation, relaxation, a sense of well being and a positive effect on mood. Tramadol is much less sedating than typical opioids, due to its effects on norepinephrine (i.e. noradrenaline).

Side effects may include miosis, constipation, nausea and vomiting, respiratory depression, myoclonus, headache, ear ringing, orthostatic hypotension, sweating, and hot flashes. Little or no significant histamine release has been observerved in studies, though itching has been reported by individuals. As with any opioid, tramadol can cause respiratory depression which can be harmful or fatal, though this is rare with tramadol, and occurs mainly in naive individuals with excessive doses. One hazard which sets tramadol apart from other opioids is the very real risk of serotonin syndrome and grand mal seizure - Doses in excess of 400mg in 24 hours is likely to provoke seizures and in severe cases death.


Synethetic opioid analgesic with prototype morphine like effects. Etonitazene is not used medically but is used in research on the opioid receptors.

Etonitazene is a benzomidazole compound, molecularly distinct from other opioids. It is closely related to the opioid clonitazene; both are derived from the parent compound nitazene.

Etonitazene is an ethoxy derivative of nitazene while the latter is a chlorine derivative. The related compound clonitazene is roughly 3x as potent as morphine, while the parent compouns is 2x as potent as morphine.

Its potency is similar to fentanyl as an analgesic in humans, but may be at least 10 or 15x greater than fentanyl in animals. Acts predominantly at the mu receptor as an agonist with high efficacy and affinity.

Has been manufactured clandestinely and sold as a heroin alternative. Due in part to its unique structure and therefore ambiguous legal status; as well as the relative ease in obtaining the precursors. It was identified on the illicit market in Moscow in 1998.

Administered by intranasal, parenteral and possibly oral routes. Has been smoked, snorted and injected by casual users.


Racemic Tilidine
Tilidine is a synthetic opioid. It is used in some countries, excluding the US, as an analgesic for moderate pain and for the treatment of restless legs. The drug is available itself under the trade names Tilidin and Valoron, or as a combination of tilidine with naloxone, under the brand name Valoron N.

Tilidine is a mild to moderately strong analgesic. It can be taken by the oral, rectal, or parenteral routes, but is most often used orally. The typical dose is 50-100mg, which is equianalgesic to around 10-20mg of oral morphine. The effects of this drug are due mainly to its N-demethylated metabolites nortilidine and bisnortilidine.

Tilidine has an atypical structure, different from most commonly referenced opioids. Chemically it can be considered a substituted arylcyclohexylamine (or more specifically, phenylcyclohexenamine) - its closest relative of the opioid family being tramadol.

Sunday, December 5, 2010

Drug History Timeline Pt 3 (Patent Medicine Era)


Throughout the 19th and early 20th century, most opium laws were aimed specifically at the chinese, and limited to the drug forms and routes of administration associated with the immigrants; the opiate patent medicines and non-smoking routes employed by the white community went largely unaffected. (up to the early 1900's)

As morphine dependence with intravenous use becomes common, an anti morphine campaign is launched and distributes free samples of heroin to morphine addicts as a non addictive substitute. (1900s)

Heroin dependence becomes prevalent and causes concern among physicians, white christians, & congress. (1900's)

Cocaine use is rampant, and racial tensions are high (1900-1914): During the first decade or more of the 1900's, cocaine had began building a reputation. Its use was particularly popular with the negroes of the south. Cocaine was rumoured to "make all men feel worthy". One man had said, "It makes working men feel like millionaires, which they're not!". This was alarming to many people in the South, who felt threatened by the prospect of their negroes copping drug induced egos and forgetting their inferior status. Some states pass their own cocaine laws, however, there was some initial resistance encountered to federal laws, particularly on States Rights grounds (the states rights doctrine was an issue of particular national attention at this time), sensational stories appeared in the press featuring cocaine crazed negroes raping white women; this was sufficient to sway any resistance.

After tireless campaigning against opium smoking, US Congress passes federal law banning opium smoking. (1905)

The Pure Food & Drug Act requires labeling of the narcotics and dosages present in patent medicines. (1906)

US government bans importation of opium. (1909)

Under the guidance of Episcopal Bishop Brent, Dr. White, and President Roosevelt, the US organizes an International Opium Commission in Shang Hai, unofficially urging governments to control opiate use. The US is set to convince other nations that the non medical use of opium is immoral and evil, meriting its worldwide criminalization. (1909)


Pre-International Opium Convention at Shanghai. Among the attendees were most of the Nations involved in far east trade. The US and other nations were eager at this time to break Britain's monopoly of trade with China, by promoting regulations on international opium trade. Nothing is agreed upon at this convention, and a larger convention is scheduled to take place in the next few years; where major global powers will discuss the opium trade.

International Opium Convention finally meets at the Hague, and this time rather than informal resolutions, a Treaty is officially signed by 13 nations, who agree to establish their own domestic controls on opium & opiates. (1912)

Next Section Here (Transition, Taxation, Prohibition Era)

The Monoamine Systems

An overview of the serotonin, norepinephrine, and dopamine systems and their functions:

The serotonin system is known to play a role in mood, emotion, social disposition, sleep cycle, wakefulness, dreaming, appetite, spinal pain modulation, and endogenous opioidergic tone. The raphe nuclei (or RN) is a medium sized cluster of nuclei located in the brainstem, and is the primary source of serotonin for the brain. The RN projects serotonergic pathways up through areas of the cerebral cortex, and downward to the dorsal horn of the spinal cord. Most modern antidepressants (zoloft, paxil, prozac) enhance central serotonergic tone, through action within the raphe nuclei and its projections in other brain areas. As a general rule of thumb, 5HT levels are highest during ones wakeful hours, and lowest during sleep. Prolonged wakefulness is known to enhance serotonergic tone - the effects of sleep deprivation are similar to the effects of serotonergic antidepressants.

The norepinephrine system plays a role in wakefulness, alertness, energy, arousal, and motivation. The locus coeruleus (or LC), a nucleus located in the pons area of the brainstem, acts as a central headquarters to the norepinephrine system. The LC produces and projects NE to areas of the hindbrain, forebrain, spinal cord and elsewhere, through a system of far reaching noradrenergic projections. It plays a major role in function of the sympathetic nervous system, during states of agitation or stress. The LC, and the adrenergic pathways projecting from it, form what is known as the LC-noradrenergic system. Activation of the LC induces a state of arousal (i.e. stress response, fight or flight mode). Plenty of drugs with sedative or anxiolytic properties suppress activity of the LC (i.e. opioids, benzodiazepines, clonidine).

The dopaminergic system plays a role in psychological reward, motivation, desire, addiction, pleasure (hedonic tone), learning, and motor fine tuning. The central component of the dopaminergic system is the ventral tegmental area (or VTA). The VTA produces dopamine, and innervates the brain with dopaminergic pathways. The VTA projects dopamine to areas of the brain as a way of rewarding certain behaviors, especially those which are evolutionarily essential (such as eating and sex), but also other behaviors which must be reinforced in order to become learned by the brain. The VTA and the pathways it projects form what is known as the mesocorticolimbic system (meso refers to midbrain, while cortico refers to cerebral cortex). Dopamine and the limbic system (with the help of neuroplastic adaptation) are essential in forming complex behavioral/sensory/environmental-memory connections as well as emotional-memory connections. The VTA forms a connection with a key pleasure center known as the nucleus accumbens. Dopamine release into the nucleus accumbens is a common trademark of rewarding and addictive behaviors.

Thursday, December 2, 2010

Introduction to Psychedelic Drugs

A psychedelic compound is, generally speaking, a psychoactive drug whose main action is to alter cognition and perception. Psychedelics are distinct from other psychoactive drugs in that they alter the mind, whereas other drugs like opiates or stimulants alter the mood. Psychedelics affect the nature of consciousness itself and access otherwise unknown states of consciousness, as opposed to affecting the degree or extent of ones consciousness and inducing familiar moods such as happiness, excitement, anxiety or apathy. Also important to note; while compounds such as heroin, morphine, cocaine, or methamphetamine are typically capable of producing addiction and physiological dependence, most psychedelics are not likely to produce either (although we all know that basically anything, including eating food, can lead to psychological or emotional dependence).

The psychedelic class covers a large family and wide spectrum of psychoactive compounds which induce a spectrum of psychedelic effects ranging from trance-like meditative states, to hallucinations, dissociation, and temporary loss or distortion of self-awareness. For this reason, the term "psychedelic" is used in a very broad or generalized context. The psychedelic category consists of multiple specific drug classes, including but not limited to hallucinogens (LSD), deleriants (atropine), empathogens (MDMA), entheogens (peyote), or dissociatives (ketamine).