Accurate Education – Marijuana (Cannabis): Terpenes – Limonene

As the name itself implies, limonene has a citrus-like scent that resembles lemons and can be found in the rinds of all citrus fruits, including lemons, limes, oranges and grapefruit which contain large amounts of this compound.

Cannabis Strains High in Limonene

Limonene is the second most abundant terpene in cannabis, but it is not necessarily found in all strains. Strains that have “lemon” or “sour” in their name are usually rich in limonene. The following strains are noted to have limonene as one of the most dominant terpenes and recommended for anxiety:

• Banana MAC
• Black Cherry OG*
• Chem OG *
• Chiesel
• Citral Glue
• Crescendo RBX1
• Girl Scout Cookies
• Ghost OG
• Grease Monkey
• O.G. Kush
• Lumpy Space Princess*
• Mandarin Cookies*
• Member Berry
• Member OG
• Military Chocolate
• Morockin’ Kush
• Pillow Factory*
• Super Lemon Haze
• Titty Sprinkles

* Indicates the strain’s the most dominant terpene is limonene

Proposed Therapeutic Benefits

Proposed therapeutic benefits of limonene include  anti-inflammatory, gastro-protective, anti-nociceptive, anti-tumor, and neuroprotective activity, mood enhancement and stress reduction as well as sedation and immune-stimulation. Confirmatory evidence in humans was found in a clinical study in which hospitalized depressed patients were exposed to citrus fragrance in ambient air demonstrated subsequent normalization of depression and successful discontinuation of antidepressant medications in 9/12 patients.

Anxiety

While THC is believed to drive most of marijuana’s pharmacodynamic effects, the entourage theory asserts that other constituents in marijuana interact with THC in ways to impact its therqpeutic effects.  THC is kown to have the side effect of anxiety and paranoia, especially at higher doses. A 2024 study assessed whether  d-limonene reduces  these side effects of THC.

The double-blind study evaluated 20 participants when they inhaled vaporized THC alone (15mg or 30mg), d-limonene alone (1mg or 5mg), the same doses of THC and d-limonene together, or placebo. Another subset of 12 participants inhaled 30mg THC+15mg d-limonene.

When d-limonene was administered alone, outcomes did not differ from placebo. However, when d-limonene was administered with THC, anxiety effects associated with THC use decreased as the d-limonene dose increased. Administration of 30mg THC+15mg d-limonene significantly reduced ratings of “anxious/nervous” and “paranoid” compared with 30mg THC alone.The effects of d-limonene were dose related and correlated with blood levels.. D-limonene did not alter THC pharmacokinetics. Additional research is needed to determine whether this benefit extends to oral use as well.

Pain

Although limonene has been widely studied and reported to have strong anxiolytic and anti-inflammatory properties, very limited information is available about its analgesic effects based on preclinical, animal research. When prophylactically used against chemical irritant–induced pain, limonene appears to be an effective analgesic. In other animal studies oral limonene was moderately effective at reducing mechanical allodynia but ineffective at blocking cold allodynia.

Although these positive results from limited studies on limonene in several chemical and neuropathic pain models, other animal research is ambiguous on whether limonene is an effective analgesic. It appears that limonene does not reduce thermal measures of pain such as hot-plate and cold allodynia, but shows effectiveness against inflammatory and neuropathic mechanical allodynia pain. Of note, there is no definitive clinical evidence available supporting these purported pain benefits in humans, either inhaled or with oral use.

Depression

A clinical study in which hospitalized depressed patients were exposed to citrus fragrance in ambient air demonstrated improved depression but more studies are needed.

Proposed Mechanisms of Action

Limonene does not interact with CB1 or CB2 cannabinoid receptors but it boosts levels of serotonin and dopamine, thought to be responsible for the anxiolytic, anti-stress, and sedative effects of the CBD. Studies of citrus oils in mice demonstrate limonene increases serotonin in the prefrontal cortex and dopamine in the hippocampus mediated via serotonin receptor, 5-HT1A.