Memory reconsolidation is an important concept that probably has a lot to do with what psychotherapy is physically doing to the brain.
Memory reconsolidation is the process of previously consolidated memories being recalled and actively consolidated. It is a distinct process that serves to maintain, strengthen and modify memories that are already stored in the long-term memory. Once memories undergo the process of consolidation and become part of long-term memory, they are thought of as stable. However, the retrieval of a memory trace can cause another labile phase that then requires an active process to make the memory stable after retrieval is complete. It is believed that post-retrieval stabilization is different and distinct from consolidation, despite its overlap in function (e.g. storage) and its mechanisms (e.g. protein synthesis). Memory modification needs to be demonstrated in the retrieval in order for this independent process to be valid.
The idea is that memories are stored in the strengths of connections among the cells, and your brain is different now than it was when a memory was first stored. Putting the memory back requires additional filing work. Maybe you’ll dream about it…
There’s controversy about using cannabis for PTSD, but there’s a completely rational basis for looking into it, involving reconsolidation. Note that a formulation of THC + CBD has already been made by pharmaceutical companies under the name Sativex.
Δ(9)-tetrahydrocannabinol (THC) and cannabidiol (CBD) are the major constituents of the Cannabis sativa plant, which is frequently consumed by subjects exposed to life-threatening situations to relief their symptomatology [sic]. It is still unknown, however, whether THC could also affect the maintenance of an aversive memory formed at that time when taken separately and/or in conjunction with CBD. The present study sought to investigate this matter at a preclinical level. We report that THC (0.3-10mg/kg, i.p.) was able to disrupt the reconsolidation of a contextual fear memory, resulting in reduced conditioned freezing expression for over 22 days. This effect was dependent on activation of cannabinoid type-1 receptors located in prelimbic subregion of the medial prefrontal cortex and on memory retrieval/reactivation. Since CBD may counteract the negative psychotropic effects induced by THC and has been shown to be a reconsolidation blocker, we then investigated and demonstrated that associating sub-effective doses of these two compounds was equally effective in attenuating fear memory maintenance in an additive fashion and in a dose ratio of 10 to 1, which contrasts with that commonly found in C. sativa recreational samples. Of note, neither THC alone nor CBD plus THC interfered with anxiety-related behaviors and locomotor activity, as assessed in the elevated plus-maze test, at a time point coinciding with that used to evaluate their effects on memory reconsolidation. Altogether, present findings suggest a potential therapeutic value of using THC and/or CBD to mitigate a dysfunctional aversive memory through reconsolidation disruption in post-traumatic stress disorder patients.
Matt Stys funnels a mound of finely ground God’s Gift, a sativa strain of marijuana, into his multicolored glass bowl and takes a hit. “It allows the images and all the things in your head to lose focus and drift away for a while,” says Stys as wisps of smoke curl from his mouth. For Stys, the images of being a noncommissioned officer running an entry control point in Iraq in 2007 and 2008 can fade away with the smoke: recollections of struggling to differentiate potential combatants from Iraqi citizens, of watching the wounded and dead flowing through his security checkpoint. Other demons in his head can waft away too, like the memories of spending his teenage years in foster care, and the moral ache of questioning the war in which he fought.
BACKGROUND AND PURPOSE:
Cannabidiol (CBD) is a non-psychotomimetic compound from Cannabis sativa which induces anxiolytic- and antipsychotic-like effects in rodents. These effects could be mediated by facilitation of the endocannabinoid system or by the activation of 5-HT(1A) receptors. As either of these mechanisms could promote adaptation to inescapable stress, the aim of the present work was to test the hypothesis that CBD would attenuate the autonomic and behavioural consequences of restraint stress (RS). We also investigated if the responses to CBD depended on activation of 5-HT(1A) receptors.
Male Wistar rats received i.p. injections of vehicle or CBD (1, 10 or 20 mg kg(-1)) and 30 min later were submitted to 60 min of restraint where their cardiovascular responses were recorded. The protocol of the second experiment was similar to the first one except that animals received i.p. injections of the 5-HT(1A) receptor antagonist WAY100635 (0.1 mg kg(-1)) before CBD treatment and exposure to restraint. 24 h later they were also tested in the elevated plus-maze (EPM), an animal model of anxiety.
Exposure to RS increased blood pressure and heart rate and induced an anxiogenic response in the EPM 24 h later. These effects were attenuated by CBD. WAY100635 by itself did not change the cardiovascular and anxiogenic response to RS, but blocked the effects of CBD.
CONCLUSION AND IMPLICATIONS:
The results suggest that CBD can attenuate acute autonomic responses to stress and its delayed emotional consequences by facilitating 5-HT(1A) receptor-mediated neurotransmission.
Posttraumatic stress disorder (PTSD) is an incapacitating syndrome that follows a traumatic experience. Predator exposure promotes long-lasting anxiogenic effect in rodents, an effect related to symptoms found in PTSD patients. Cannabidiol (CBD) is a non-psychotomimetic component of Cannabis sativa with anxiolytic effects. The present study investigated the anti-anxiety actions of CBD administration in a model of PTSD. Male Wistar rats exposed to a predator (cat) received, 1 h later, singled or repeated i.p. administration of vehicle or CBD. Seven days after the stress animals were submitted to the elevated plus maze. To investigate the involvement of 5HT1A receptors in CBD effects animals were pre-treated with WAY100635, a 5HT1A receptor antagonist. To explore possible neurobiological mechanisms involved in these effects, 5HT1A receptor mRNA and BDNF protein expression were measured in the hippocampus, frontal cortex, amygdaloid complex and dorsal periaqueductal gray. Repeated administration of CBD prevented long-lasting anxiogenic effects promoted by a single predator exposure. Pretreatment with WAY100635 attenuated CBD effects. Seven days after predator exposure 5HT1A mRNA expression was up regulated in the frontal cortex and hippocampus. CBD and paroxetine failed to prevent this effect. No change in BDNF expression was found. In conclusion, predator exposure promotes long-lasting up-regulation of 5HT1A receptor gene expression in the hippocampus and frontal cortex. Repeated CBD administration prevents the long-lasting anxiogenic effects observed after predator exposure probably by facilitating 5HT1A receptors neurotransmission. Our results suggest that CBD has beneficial potential for PTSD treatment and that 5HT1A receptors could be a therapeutic target in this disorder.
Community-based studies suggest that cannabis products that are high in Δ⁹-tetrahydrocannabinol (THC) but low in cannabidiol (CBD) are particularly hazardous for mental health. Laboratory-based studies are ideal for clarifying this issue because THC and CBD can be administered in pure form, under controlled conditions. In a between-subjects design, we tested the hypothesis that pre-treatment with CBD inhibited THC-elicited psychosis and cognitive impairment. Healthy participants were randomised to receive oral CBD 600 mg (n=22) or placebo (n=26), 210 min ahead of intravenous (IV) THC (1.5 mg). Post-THC, there were lower PANSS positive scores in the CBD group, but this did not reach statistical significance. However, clinically significant positive psychotic symptoms (defined a priori as increases ≥ 3 points) were less likely in the CBD group compared with the placebo group, odds ratio (OR)=0.22 (χ²=4.74, p<0.05). In agreement, post-THC paranoia, as rated with the State Social Paranoia Scale (SSPS), was less in the CBD group compared with the placebo group (t=2.28, p<0.05). Episodic memory, indexed by scores on the Hopkins Verbal Learning Task-revised (HVLT-R), was poorer, relative to baseline, in the placebo pre-treated group (-10.6 ± 18.9%) compared with the CBD group (-0.4% ± 9.7 %) (t=2.39, p<0.05). These findings support the idea that high-THC/low-CBD cannabis products are associated with increased risks for mental health.
BACKGROUND AND OBJECTIVES:
Social anxiety appears to be a risk factor for cannabis-related problems. Socially anxious individuals are vulnerable to using cannabis to cope in social situations and to avoiding social situations if marijuana is unavailable. Yet, the relative impact of cannabis use to cope with social anxiety relative to use to cope with negative affect more broadly has yet to be examined.
The present study used the Marijuana to Cope with Social Anxiety Scale (MCSAS) to examine the incremental validity of using cannabis use to cope in social situations (MCSAS-Cope) and avoidance of social situations if cannabis is unavailable (MCSAS-Avoid) in a community-recruited sample of 123 (34.1% female) current cannabis users.
After controlling for age of first cannabis use, gender, alcohol and tobacco use, other cannabis use motives, and cannabis expectancies, MCSAS-Cope remained significantly positively related to cannabis use frequency and cannabis-related problems. After controlling for age of first cannabis use, gender, alcohol and tobacco use, and experiential avoidance, MCSAS-Avoid remained significantly related to cannabis problems but not frequency.
DISCUSSION AND CONCLUSIONS:
The present findings suggest that cannabis use to manage social forms of anxiety may be important to understanding cannabis use behaviors.
The current findings identify cognitive/motivational factors implicated in more frequent cannabis use and in cannabis-related impairment, which may be essential to inform efforts to further refine prevention and treatment efforts.
The drug 3,4 methylenedioxymethamphetamine (MDMA; ecstasy) has a widely documented ability to increase feelings of love and closeness toward others. The present study investigated whether oxytocin, a neuropeptide involved in affiliative behavior, may play a role in this effect. A moderate (5 mg/kg, i.p.) dose of MDMA increased social interaction in male Wistar rats, primarily by increasing the amount of time rats spent lying adjacent to each other. MDMA (5 mg/kg) activated oxytocin-containing neurons in the supraoptic and paraventricular nuclei of the hypothalamus, as shown by Fos immunohistochemistry. MDMA (5 mg/kg i.p.) also increased plasma oxytocin levels and this effect was prevented by pre-treatment with the 5-HT(1A) antagonist N-[2-[4-(2-methyoxyphenyl)-1-piperazinyl]ethyl]-N-2-pyridinylcyclohexanecarboxamide maleate salt (WAY 100,635; 1 mg/kg i.p.). The oxytocin receptor antagonist tocinoic acid (20 microg, i.c.v.) had no effect on social behavior when given alone but significantly attenuated the facilitation of social interaction produced by MDMA (5 mg/kg). The 5-HT(1A) agonist 8-hydroxy-2-(di-n-propylamino)-tetraline) (8-OH-DPAT, 0.25 mg/kg, i.p.) increased social behavior in a similar way to MDMA and this effect was also significantly attenuated by tocinoic acid. Taken together, these results suggest that oxytocin release, stimulated by MDMA through 5-HT(1A) receptors, may play a key role in the prosocial effects of MDMA and underlie some of the reinforcing effects of the drug.
Oxytocin attenuates responses to stress and threat (e.g., by fostering social approach in animals), but direct investigations of whether the hormone also facilitates approach-related social behaviors in humans are lacking. To assess approach-avoidance tendencies, we had participants respond to images of happy and angry faces with direct or averted gaze by either pulling a joystick toward themselves (approach) or pushing it away from themselves (avoidance). When given a placebo, participants’ action tendencies were typical, with happy faces eliciting approach responses and angry faces eliciting avoidance responses. However, 24 IU of oxytocin moderated these tendencies, with the inclination to approach angry faces with direct gaze being negatively related to social anxiety. The results demonstrate that oxytocin facilitates approach in humans in response to social threat, which verifies its anxiolytic potential. Moreover, they underscore the moderating role of dispositional factors reported in endocrine research and their therapeutic implications.
The limonene in a lot of common cannabis strains is also a 5-HT1A agonist, as noted in an earlier post.
It’s almost like people are competently self-medicating, by the same standards applied to pharmaceutical drugs. You can go to a bar, and that’s normal behavior. You can go to a psychiatrist for benzodiazepines if you’re anxious or can’t sleep. Smoking weed with friends is pathological, because drugs acting at CB1 receptors are fundamentally different from drugs acting at GABA-A receptors or eating an orange.
Not to mention that the peripheral anti-inflammatory effects probably also cause you to feel subjectively better.
Daily, constant cannabis smoking is a thing for pharmacokinetic reasons. There are also psychiatric drugs you might take 2-3 times each day, especially in instant-release formulations. THC and CBD are also competitively inhibiting FAAH, so they’re roughly like acetylcholinesterase inhibitors, but for endocannabinoids, which also act at vanilloid receptors (like capsaicin). Some people dislike using cannabis orally because of unpredictable dosing, and also because the 11-hydroxy-THC produced by the liver changes the nature of the experience. Smoking gives much finer control over the length and intensity of the experience, although the fact of frequently repeating the behavior makes it harder to stop.
Workplace distractions, multi-tasking, and sleep-deprivation can all be more cognitively impairing than cannabis, especially with tolerance and a well-selected strain. You could get fired for being high at work, but work itself promotes sleep-deprivation by subsidizing coffee, expecting people to look at screens with blue light late at night, etc. Open offices promote distraction. That is, completely normal parts of office environments are impairing mental performance worse than being a little bit drunk or high on the job. This is objectively the case.
Traumatized people get locked into cages all alone and/or raped for smoking cannabis to deal with their earlier, apparently insuffient trauma. Drug dealers selling cannabis were doing more for their communities than the many people selling alcohol.
“Drug abuse” is just a really dumb way of talking about what most people are doing when they’re using cannabis. Most people don’t even smoke every day. We aren’t gaining anything by replacing the word “fun” with “abuse potential.” The pharmacology matters. In the long run, science undermined the ideological justification for the drug war. The truth is indeed setting people free from jail (Obama plans to release some people early).
This is also a case where postmodernism isn’t completely frivolous. The power of drug war rhetoric is extraoardinary. For many people, I imagine there’d be extreme resistance to accepting the facts in this post. The benefits of cannabis aren’t news to the people who like to smoke it. It was local knowledge, a marginalized discourse. The scientists, a different group of people, can say the same things and they’ll be accepted as true, because the necessary rituals and sacrifices were performed. “Sacrifice” is a common euphemism for euthanasia. Like, if your rats are sick or you’re done with them and don’t need tissue, you write “SAC” on a post-it note and stick it on the cage. The vet staff will come through and asphyxiate the rats in marked cages with carbon dioxide. I was of the opinion that halothane or isoflurane were more humane for that purpose. While science is special in some ways, it might as well be magic to most people. It’s as if the scientists were consulting an oracle. Their oracle says it’s bad, but the bad people doing the bad thing say the truth can be experienced for ourselves. It’s a political matter of deciding what qualifies someone to have an opinion.