# Anti-inflammatory

Anti-inflammatory or antiphlogistic is the property of a substance or treatment that reduces inflammation or swelling. Anti-inflammatory drugs, also called anti-inflammatories, make up about half of analgesics. These drugs remedy pain by reducing inflammation as opposed to opioids, which affect the central nervous system to block pain signaling to the brain.

## Drugs
### Nonsteroidals

Nonsteroidal anti-inflammatory drugs (NSAIDs) alleviate pain by counteracting the cyclooxygenase (COX) enzyme. On its own, COX enzyme synthesizes prostaglandins, creating inflammation. In whole, the NSAIDs prevent the prostaglandins from ever being synthesized, reducing or eliminating the inflammation and resulting pain.
Some common examples of NSAIDs are aspirin, ibuprofen, and naproxen. The newer specific COX-inhibitors are not classified together with the traditional NSAIDs, even though they presumably share the same mode of action.
On the other hand, there are analgesics that are commonly associated with anti-inflammatory drugs but that have no anti-inflammatory effects. An example is paracetamol (known as acetaminophen in the U.S). Contrary to NSAIDs, which reduce pain and inflammation by inhibiting COX enzymes, paracetamol has—as early as 2006—been shown to block the reuptake of endocannabinoids, which only reduces pain, likely explaining why it has minimal effect on inflammation; paracetamol is sometimes combined with an NSAID (in place of an opioid) in clinical practice to enhance the pain relief of the NSAID, while still receiving the injury/disease modulating effect of NSAID-induced inflammation reduction (which is not received from opioid/paracetamol combinations).

#### Side effects

Long-term use of NSAIDs can cause gastric erosions, which can become stomach ulcers and in extreme cases can cause severe haemorrhage, resulting in death. The risk of death as a result of GI bleeding caused by the use of NSAIDs is 1 in 12,000 for adults aged 16–45. The risk increases almost twentyfold for those over 75. Other dangers of NSAIDs are exacerbating asthma and causing kidney damage. Apart from aspirin, prescription and over-the-counter NSAIDs also increase the risk of heart attack and stroke.

### Corticosteroids

Corticosteroids, specifically glucocorticoids or glucocorticoid receptor agonists, are powerful anti-inflammatory agents, but they are also powerful immunosuppressants and are associated with various toxicities, which constrains their use.

### Antileukotrienes

Antileukotrienes are anti-inflammatory agents which function as leukotriene-related enzyme inhibitors (arachidonate 5-lipoxygenase) or leukotriene receptor antagonists (cysteinyl leukotriene receptors), and consequently oppose the function of these inflammatory mediators. Although they are not used for analgesic benefits, they are widely utilized in the treatment of diseases related to inflammation of the lungs, such as asthma and COPD, as well as sinus inflammation in allergic rhinitis. They are also being investigated for use in diseases and injuries involving inflammation of the brain (e.g., Parkinson's disease).

### Serotonergic psychedelics

Various serotonergic psychedelics, acting as serotonin 5-HT$_{2A}$ receptor agonists, have been found to be powerful and highly potent anti-inflammatory and immunomodulatory agents. In contrast to corticosteroids however, psychedelics with anti-inflammatory effects do not suppress the immune system. Some psychedelics are far more potent in their anti-inflammatory effects than in their psychedelic effects. For instance, (R)-DOI is 30- to >50-fold more potent in producing anti-inflammatory effects than in producing psychedelic-like behavioral effects in preclinical research. Psilocin, the active form of psilocybin, has similar anti-inflammatory potency as (R)-DOI.
The potencies of psychedelics and other serotonin 5-HT$_{2A}$ receptor agonists as anti-inflammatory drugs vary, with 2C-I, DOIB, 2C-B, 4-HO-DiPT, DOI, 2,5-DMA, DOET, DOM, psilocin, and 2C-H being highly potent and fully efficacious anti-inflammatories; TMA-2, 2C-B-Fly, TCB-2, ETH-LAD, LSD, and 2C-T-33 being partially efficacious anti-inflammatories; and lisuride, 1-methylpsilocin, 5-MeO-DMT, and DMT having negligible efficacy.
Both non-hallucinogenic agents with full anti-inflammatory effects, such as 2,5-DMA, and non-anti-inflammatory agents with full psychedelic effects, such as DOTFM, are known. Hence, the psychedelic and anti-inflammatory effects of serotonin 5-HT$_{2A}$ receptor agonists appear to be fully dissociable. These effects appear to be mediated by different intracellular signaling pathways, although the exact pathways are still under study.
Serotonin 5-HT$_{2A}$ receptor agonists with anti-inflammatory effects but reduced psychedelic effects, such as 2C-iBu (ELE-02), are under development for the treatment of inflammatory conditions. They may also have applications in the treatment of neuroinflammation. The anti-inflammatory effects of psychedelics may be involved in the effects of psychedelic microdosing. Relatedly, LSD microdosing is being studied in the treatment of Alzheimer's disease for its anti-inflammatory effects.
Although some psychedelics have anti-inflammatory effects, many psychedelics are also potent serotonin 5-HT$_{2B}$ receptor agonists. This action, with repeated long-term use, has been implicated in the development of cardiac fibrosis and valvulopathy. This may also be the case with microdosing. However, the risks are theoretical, and more research is needed to see if these complications can actually occur with psychedelics. A preliminary animal study found that chronic microdosing of LSD did not result in heart structure changes or valvulopathy in rodents. Research appears to be mixed on whether LSD and psilocin are potent serotonin 5-HT$_{2B}$ receptor agonists or not.