Heroin, also known as Diacetylmorphine, is a semi-synthetic opioid ester derived from morphine which in recent years has played a large role in precipitating the “Opioid Crisis” in America. This is in part due to the large number of highly addictive opioid painkillers which were heavily prescribed beginning in the mid 1990’s and early 2000’s. Being cross-tolerant to heroin, any user who was addicted to painkillers could use heroin to produce the same euphoric and analgesic (pain suppression) effects and to stave off withdrawal. This is compounded by the fact that heroin is typically cheaper per dose than any prescribed opioid, prompting a migration from prescription painkillers towards heroin.
How Heroin Effects The Body
Heroin acts a general Central and Peripheral Nervous System depressant. Depending on the route of intake, heroin can have very different and distinct pharmacodynamic profiles. For example, when eating heroin it will be broken down completely into Morphine through first pass metabolism and will not produce the same intensity or depth of euphoria typically associated with heroin use. This will result in the same effects as if you had taken a pill of Morphine. On the other hand, smoking heroin seems to produce the same type and intensity of high as injection, however the onset of euphoria is delayed slightly. As far as the effects of snorting heroin, there have not been many controlled studies done with this intake method, but anecdotal evidence seems it is similar in pharmacodynamics to IV use, but less intense and stretched out over a longer duration.
When you use heroin by shooting it up it will be broken down in the brain, liver, and kidneys into several different metabolites through hydrolysis, the most reactive of which are 6-Monoacetylmorphine (6-MAM) and Morphine (MOR) with the conjugates Morphine-6-Glucuronide (M6G) and Morphine-3-Glucuronide (M3G)¹. It should be noted that heroin itself is biologically inactive, and acts as a prodrug delivery system for its more active metabolites like 6-MAM and MOR.
Due to their chemical structure, Morphine-derived esters like heroin are able to penetrate the Blood Brain Barrier much more rapidly (about 10 times faster) than Morphine itself and are thus much more immediate and potent in their effects¹. Once in the brain, heroins derivative metabolites bind to the μ (Mu), δ (Delta), and κ (Kappa) opioid receptors and act as an agonist (an activity or function promoter).
How Heroin Effects The Brain
The μ, δ, and κ opioid receptors in the brain, spinal cord, and gastrointestinal tract act as receivers for opioid peptides that are naturally produced by the body . There are 3 classes of endogenous opioid peptides: Enkephalins (Leu-Enkephalin and Met-Enkephalin), Beta-Endorphin, and Dynorphins. These are called “opioid” peptides only because opiates/opioids bind to the same receptors as the peptides themselves. Beta-Endorphin and Dynorphin may also be referred to as “Endorphins” as a contraction of endogenous morphines. Heroin is able to hijack this system of receptors because it has a higher binding affinity to the receptors than the endogenous opioid peptides. This means it can activate the receptors with a much higher intensity and duration than endogenous peptides and will thus produce a much greater neuro/physiological effect¹. While heroin does affect all 3 opioid receptors, there is a much higher proclivity for μ-opioid receptor agonist action.
The μ-opioid receptors most readily bind with Beta-Endorphin and are thought to affect the limbic system (reward center)¹, physical addiction¹, blockade of pain signals in the brain, analgesia of acute pain, and produce euphoria. The δ-opioid receptors in the Limbic System which naturally bind most readily with Enkephalins are thought to be responsible for analgesia of chronic pain, regulation of memory and emotional condition, sensations of hunger and thirst, and has a large impact on gastrointestinal function¹. The κ-opioid receptors naturally bind most readily with Dynorphin and are thought to involve anxiety and addiction like behavior as well as an ability to produce hallucinations and dissociative effects¹. Endorphins & Enkephalins are mainly utilized to moderate pain signals in the brain. Endorphins achieve this via action in the brain stem, while Enkephalins act in the spinal cord. Heroin’s strong binding to these sites is responsible for slowing gastrointestinal peristalsis and function to a crawl, slowed heart rate, severe breathing depression, cough suppression, pupil constriction, as well as a massive analgesic effect¹.
The slowing of vital functions is achieved through modulation of descending nerve pathways (from the brain to the body), while the analgesia is produced by a cascade effect in Afferent Nociceptive (AN) nerve fibers. AN fibers convey information from the body to the brain through the peripheral nervous system and spinal cord. The slowed vital functions and effect of analgesia are produced through stimulation of GABA (Gamma-Aminobutyric Acid; an inhibitory neurotransmitter) release in both descending and AN neurons which subsequently reduces the amount of Dopamine (an excitatory neurotransmitter) released during nerve signal conveyance¹. This has the effect of dampening both the descending pathway signals to motor neurons resulting in slowed vital functions and the inbound signals from AN fibers which reduces the amount of pain or discomfort felt.
When heroin is present in the brain, the body will respond by decreasing production of endogenous opioids. Once heroin has been used for an extended time, usually about 3 to 4 weeks, the brain will begin adapting by decreasing production of endogenous opioid peptides by a substantial amount. This means that the brain will be unstable without the continued presence of the exogenous (introduced from outside the body) opioids provided by continued heroin use. This has the effect of creating chemical dependence. Without continued introduction of exogenous opioids, you will begin to go into heroin withdrawal.