What are the Short- and Long-Term Effects of Heroin?

The method validation and analysis for the blood and brain tissue samples were performed with a Waters Quattro Premier XE MS/MS using the same instrumental parameters as for dialysate (Gottas et al., 2012), with some modifications. Data were processed with the TargetLynx program (Waters, Milford, MA, USA), using peak area for quantification. Calibration curves with five to seven points were applied for the analytes. The lowest level of quantification (LLOQ) and lowest level of detection (LOD) are presented in Table ​Table2.2.

Brain ECF pharmacokinetics

MORs mediate the rewarding and reinforcing effects of heroin and morphine (Johnson and North, 1992) (for reviews see Koob and Bloom, 1988; Feltenstein and See, 2008). Brain striatum, which has a high abundance of κ-opioid receptors and MORs (Kling et al., 2000), plays an important role regarding the effects seen after use of drugs of abuse (Everitt and Robbins, 2005). Further, in order to measure opiate concentrations in brain ECF for 1 min sampling periods and to get adequate recovery measurements, it was essential to use a 4 mm microdialysis membrane. The rat striatum allows the use of such long dialysis probe in a relative homogenous area.

Heroin Addiction

The within-day and between-day precision and accuracy (Table ​(Table3)3) showed a good precision and accuracy for the analytical method. The transition from heroin use to addiction is a complex process deeply rooted in the brain’s neurochemistry. Repeated heroin use leads to significant changes in the brain’s reward system, altering the balance of neurotransmitters and the sensitivity of neural pathways. The opium poppy was cultivated in lower Mesopotamia as long ago as 3400 BC.86 The chemical analysis of opium in the 19th century revealed that most of its activity could be ascribed to the alkaloids codeine and morphine. Something else that’s related to the topic of the heroin molecular structure is drug testing. With traditional drug testing panels, it may be possible to see whether someone uses opioids, but not whether it’s specifically heroin that they’re testing positive for.

• The pharmacokinetics of heroin will be discussed for each route of administration.
• Accordingly, they also question the generalization of numerous neurobiological studies using morphine, to also account for mechanisms involved in heroin-related effects.
• The log-transformed concentration versus time plots were used to assess the distribution (α) and elimination phase.

Figures

Naloxone-precipitated symptoms are in fact more severe after repeated M6G administration than after morphine 128. Bolus administration of heroin to rats indicated a rapid metabolism of heroin before it reached the brain, suggesting that 6-MAM was the main substance transported over the BBB shortly after i.v. These results extended previous observations in our laboratory, in experiments where heroin was given s.c. (Andersen et al., 2009; Boix et al., 2013), showing that 6-MAM is the dominating compound in blood and brain also after rapid i.v.

Indeed, brain levels of 6-MAM are reduced by anti-6-MAM mAb to a lesser extent after heroin administration than after 6-MAM administration 173. As can be observed in Figure ​Figure3,3, heroin entered the brain ECF quickly and attained a Cmax already 1.5 min after the i.v. At this point in time, the brain ECF 6-MAM concentration was already of the same order of magnitude and continued to rise thereafter, reaching the Cmax 4.3 min after the heroin injection when almost no heroin was found in the brain ECF. Thus, the brain ECF 6-MAM concentrations appeared to reflect the 6-MAM concentrations in the blood, both with respect to time course and concentrations, and not the brain ECF concentrations of heroin. Even though morphine was present shortly after heroin injection, its levels in blood and brain were much lower than for heroin and 6-MAM in this initial stage, and the contribution of morphine to the observed effects was probably limited.

Pertinent Studies and Ongoing Trials

Factors that impact the metabolism of heroin metabolites include genetic factors, medical conditions and other individual factors. Metabolism of opioids like heroin may be slower or less efficient in older people, or people who are considered medically compromised, particularly if they have impaired renal and hepatic function or impaired immunity. In other words, a slower metabolism means that the drug is more potent and active in the body for longer periods, so opioids like heroin can be dangerous for people with these conditions. Injection in humans, heroin peaks at 30 s in the arterial blood (and presumably in the brain) 26, a timing synchronous with the characteristic heroin ‘flash’, highly desired by most users 14, 15. Although 6-MAM is produced by plasma esterases while heroin is still distributing to the brain and other peripheral compartments, heroin remains by far the prevailing opioid in the plasma for about 8 min 26.

Treatment / Management

Heroin (3,6-diacetylmorphine or diamorphine) is a semi-synthetic derivative of morphine, a naturally occurring opiate contained, along with codeine, in the latex of the opium poppy (Papaver somniferum). The opium poppy was first domesticated circa 6000 B.C.E. in Europe, and its cultivation spread eastwards over the following millennia 1, 2. It is worth noticing that the frequent reference in textbooks and journal articles to a supposed initial spread of opium production from Mesopotamia has long been shown to be based on flawed scholarship 2, 3. While the medical use of opium in antiquity (first by Greco-Roman medicine and centuries later by Arab, Indian, and Chinese medicines) is well documented, reliable evidence of widespread ‘recreational’ use is much more recent and appears to be related to technological innovations. Technological innovations were crucial also in the case of morphine, which was isolated in 1817, but became widely used for medical and non-medical purposes only after the invention of the hypodermic syringe a few decades later 5. At present, the non-medical use of morphine is a relatively rare occurrence, compared to heroin.

Recent Activity

• As detailed in the previous section, plasma concentrations of 6-MAM remain lower than that of heroin for the first 8 min after i.v.
• The test is free, confidential, and no personal information is needed to receive the result.
• Heroin is front and center in the national spotlight for the wrong reasons.

Route 32, but its popularity varies greatly, mainly as a function of the prevailing form of street heroin available in any given region. Heroin hydrochloride (the prevailing form of street heroin in most regions of the USA) is not suitable to this route of administration because most of it is destroyed at the temperatures required for vaporization. In contrast, freebase heroin (like the brown heroin popular in Europe) vaporizes at relatively gentle heat 33. Depending on a variety of genetic and environmental factors, some people develop a disease called heroin addiction because of changes to areas of the brain that affect self-control, motivation and pleasure.

• Remarkably, when asked to guess which of the two drugs the participants had received, morphine was recognized with more accuracy than heroin.
• Within 10–45 min, heroin becomes undetectable in the blood 24–27 (Fig. ​(Fig.3).3).
• A subclass of morphine derivatives, namely the 3,6 esters of morphine, with similar effects and uses, includes the clinically used strong analgesics nicomorphine (Vilan), and dipropanoylmorphine; there is also the latter’s dihydromorphine analogue, diacetyldihydromorphine (Paralaudin).
• When animals are repeatedly exposed to one of the two chambers of a CPP apparatus while under the effects of an addictive drug, they exhibit a preference for the drug-paired chamber relative to the vehicle-paired chamber 194,195,196.
• In humans, the plasma concentration of morphine-3-sulfate is several hundred times lower than that of M3G, while morphine-6-sulfate is undetectable in most people 67.

Heroin’s Short-Term Effects on the Brain

This might be due to their shared high affinity for the same splice variant of the MOP 88. Furthermore, 6-MAM has how long does heroin stay in your system affinity for the DOP, which might contribute to its potent analgesic effect 91, 92 (Table 2). As addiction develops, the brain’s reward system becomes increasingly focused on heroin use at the expense of natural rewards.