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. Author manuscript; available in PMC: 2026 Apr 1.
Published in final edited form as: Neurosci Lett. 2025 Mar 21;854:138205. doi: 10.1016/j.neulet.2025.138205

Terpene Blends from Cannabis sativa are Cannabimimetic and Antinociceptive in a Mouse Chronic Neuropathic Pain Model via Activation of Adenosine A2a Receptors

Abigail M Schwarz 1, Caleb A Seekins 1, Omar El-Sissi 2, John M Streicher 1,3,*
PMCID: PMC12005347  NIHMSID: NIHMS2069170  PMID: 40122228

Abstract

An increase in the use of medicinal Cannabis for pain management has spurred research into the understudied bioactive compounds in Cannabis, such as terpenes. In our previous work, we showed that isolated and purified terpenes were cannabimimetic and also relieved chemotherapy-induced peripheral neuropathy (CIPN) pain via activation of Adenosine A2a Receptors (A2aR) in the spinal cord. However, terpenes are most often consumed by the public as complex extracts and mixtures, not purified individual terpenes, and whether this cannabimimetic and antinociceptive activity holds true in terpene extracts and blends is not clear. In this study, we thus extracted terpene blends from three distinct Cannabis chemovars and assessed these blends in male and female CD-1 mice for their cannabimimetic activity in the tetrad assay and pain-relieving properties in a CIPN model. Each terpene blend was unique in the relative amounts of different terpenes extracted. Though each blend was unique, each similarly elicited cannabimimetic behaviors of catalepsy, hyperlocomotion, and hypothermia, without tail flick analgesia. All three terpene blends effectively relieved CIPN, though the antinociception was more robust in male than in female mice. This antinociception was recapitulated by purified Myrcene but not D-Limonene. The A2aR antagonist istradefylline blocked the pain-relieving effects of all three terpene blends, suggesting that the terpene blends act on A2aR to relieve CIPN pain. Together, these findings suggest that terpene blends have similar pharmacological effects as purified single terpenes, and that observations made with single terpenes may be applicable to the complex terpene mixtures commonly consumed by the public.

Keywords: Terpenes, Cannabimimetic, Cannabis, Neuropathic Pain, Adenosine A2a Receptor, Analgesia

Introduction

Cannabis has had a surge in popularity within the United States in recent years for medicinal use, driven at least in part by widening legalization [27]. The primary reason individuals use Cannabis medicinally is for pain reduction/relief, followed by anxiety [11, 18, 22]. A growing interest in Cannabis as a therapeutic agent has spurred investigation into the various chemicals found within the plant, aiming to understand how these individual compounds contribute to the therapeutic effects. The different Cannabis “strains” or chemovars, which refer to the distinct varieties of Cannabis based on the chemical composition, may influence the overall therapeutic effects of Cannabis [28]. Additionally, many of the minor compounds in the plant are biologically active, and the ratios of these minor compounds may influence Cannabis’ effects [15, 29]. The most abundant and widely studied compounds in Cannabis are the cannabinoids cannabidiol (CBD) and Δ9-tetrahydrocannabinol (THC). However, other compounds, such as terpenes, play an important role in how Cannabis can be used as a therapeutic agent. Terpenes are simple hydrocarbons that provide taste and aroma to the plant, and some terpenes have been shown to have analgesic [2, 4, 13], anti-inflammatory [14, 35], and anxiolytic properties [33]. We have previously observed that the isolated and purified terpenes geraniol, linalool, α-humulene, β-pinene, and β-caryophyllene are cannabimimetic, reduce acute thermal pain, and act on both cannabinoid and non-cannabinoid receptors [13]. We also found that these terpenes are effective at relieving inflammatory pain as well as chemotherapy-induced neuropathic pain via activation of Adenosine A2a Receptors (A2aR) in the spinal cord [31].

While our previous studies were promising for suggesting the potential of terpenes for treating chronic pain, they were limited by the use of isolated and purified terpenes. Most public users of terpene products consume these ligands not as purified single terpenes, but rather complex extracts and mixtures, with or without cannabinoids present. Mixtures of terpenes may have different effects in vivo compared to isolated terpenes. Clinical data shows that patients who consumed chemovars with higher levels of the terpenes myrcene and terpinolene in Cannabis with CBD and THC self-reported stronger pain-relieving and anxiolytic effects than patients who consumed chemovars with little to no myrcene and terpinolene [37]. These results could be interpreted as evidence for the “entourage effect” which refers to the hypothesis that Cannabis compounds including terpenes may modulate phytocannabinoid effects by direct or indirect mechanisms. Our lab has noted previously that individual terpenes enhance synthetic cannabinoid activity, supporting this hypothesis [13], though other studies have evidence against the entourage effect as a phenomenon [30].

For these reasons, we sought to evaluate the pharmacological effects of three different terpene extracts from different Cannabis chemovars that mimic common varieties consumed by the public. These extracts were chosen for their wide variability in terpene composition. Sweet #50 and Fruit #18 are high myrcene varieties which commonly carry the legacy designation “indica”. Fruit #18 is similar to conventionally named Cannabis cultivars such as Purple or Kush while Sweet #50 with its high terpinolene content is most similar to Blue Dream. Sweet #45 is a high limonene variety with legacy names such as Pink Runtz or Lemon Cookies. These extracts were tested for cannabimimetic activity in the cannabinoid tetrad assay and antinociceptive effects in the chemotherapy-induced peripheral neuropathy (CIPN) model, both in mice. We thus sought to determine if different complex mixtures of terpenes had unique cannabimimetic and pain-relief behavioral effects when compared to our previous work with isolated single terpenes.

Methods

A full description of the Methods can be found in the Supplementary Materials. All animal experiments were approved by the University of Arizona IACUC, and carried out in accord with the guidelines of the NIH Guide for the Care and Use of Laboratory Animals.

Results

Chemical Analysis of Terpene Blends

As described in the Methods, we prepared 3 terpene blend extracts from 3 different chemovars of Cannabis. The three terpene blend samples contained a unique terpene profile with differing quantities and identities of major terpenes. Blends Fruit #18 and Sweet #50 had β-Myrcene as the most abundant terpene by weight at 56.94% and 56.28%, respectively, while Limonene was the most abundant terpene in Sweet #45 at 38.30% (Figure 1, Table S1). Other terpenes in abundance include α-Pinene (Fruit #18: 15.66%, Sweet #45: 4.12% and Sweet #50: 13.22%) and β-Caryophyllene (Fruit #18: 5.12%, Sweet #45: 3.66% and Sweet #50: 9.06%). Sweet #50 was the only blend to contain significant amounts of Terpinolene/Fenchone at 18.88%, with the other two blends containing < 1%. Overall, 34 terpenes were detected between the 3 blends, albeit some were at < 1% abundance. The 3 tested blends thus represent complex mixtures with key differences from each other, especially in concentrations of β-Myrcene, Limonene, and Terpinolene (Figure 1, Table S1).

Figure 1: Terpene Composition of the Blends.

Figure 1:

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Terpene content by percent of total weight shown for the three tested blends. Terpenes under 1% weight were excluded from the plot. The numeric values for all terpenes in all blends can be found in Table S1.

Terpene Blends are Cannabimimetic and Potentially Anxiogenic

We first evaluated the terpene blends in the cannabinoid tetrad assay, which is a suite of 4 behaviors (catalepsy, hypolocomotion, hypothermia, analgesia) that are associated with cannabinoid pharmacology [23]. We previously found that the isolated terpenes geraniol, linalool, α-humulene, β-pinene and β-caryophyllene elicit these behaviors to various extents; in these studies, terpene tail flick antinociception was driven by the CB1 receptor while other tetrad effects were driven by the A2aR or an unidentified additional receptor system [13]. The terpene blends were injected at a dose of 200 mg/kg, which is the same dose used in our previous terpene studies [13, 31]. We observed that all terpene blends induced significant catalepsy (Figure 2A), hypothermia (Figure 2B), and hypolocomotion (Figure 2C–D). However, none of the terpene blends elicited analgesia in the acute thermal tail flick pain model (Figure 2E). We found that mice given Sweet #45 and Sweet #50 exhibited potential anxiety-like behavior, spending less time in the center of the open field chamber than the control mice given vehicle (Figure 2F). Overall, these observations suggest that the terpene blends Fruit #18, Sweet #45, and Sweet #50 are cannabimimetic and blends Sweet #45, and Sweet #50 may also be mildly anxiogenic. These results are also broadly similar to the cannabimimetic activity observed for single, purified terpenes in our earlier work; single terpenes or the synthetic cannabinoid WIN55,212 produced much more tail flick antinociception (none here), more hypothermia, and similar catalepsy and motor suppression to our blends. Since we did not observe tail flick antinociception in response to the blends, this tetrad activity is likely driven by a non-CB1 receptor mechanism as previously shown for single terpenes [13].

Figure 2: Terpene Blends Show Cannabimimetic Tetrad Activity.

Figure 2:

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Male and female CD-1 mice were injected with 200 mg/kg of one of the terpene blends or vehicle control (10% DMSO, 10% Tween80, 80% USP saline; i.p.). The cannabinoid tetrad of behaviors (catalepsy, hypolocomotion, hypothermia, and analgesia) were measured as described in the Methods. Data is shown as the mean ± SEM overlayed with individual data points from each animal with closed symbols showing males and open symbols showing females. N = 10 mice/group.A) Catalepsy represented by % time cataleptic/immobile over 5 min (ANOVA F = 7.459, p = 0.0005). B) Hypothermia shown by body temperature (ANOVA F = 16.33, p < 0.0001). Hypolocomotion represented by the C) distance traveled in meters (ANOVA F = 8.675, p = 0.0002), and D) and the time spent mobile over the 5 min. measurement window (ANOVA F = 8.986, p = 0.0001). E) Analgesia measured by thermal tail flick thermal latency with a 10 sec cutoff (ANOVA F = 1.975, p > 0.05). F) The open-field test was used to measure anxietylike behavior; less time spent in the center of the apparatus indicates higher anxiety (ANOVA F = 3.488, p = 0.0254). Data were analyzed via One-way ANOVA, with Dunnett’s post hoc, *p<0.05, **p<0.01, ***p<0.001, ****p<0.0001 compared to Vehicle group. The blends showed 3 of the 4 tetrad behaviors in addition to potential anxiogenic activity.

Terpene Blends Relieve Neuropathic Pain Primarily in Male Mice

We have found that the isolated terpenes geraniol, linalool, α-humulene, β-pinene and β-caryophyllene effectively relieve neuropathic pain in a CIPN model [31]. We thus sought to determine if terpene blends produce similar pain relief in CIPN, and whether that pain relief differs by blend. All terpene blends produced robust timedependent antinociception in male mice as measured by time course and area under the curve (AUC)(Figure 3A). The three blends were similar to each other, however, Fruit #18 and Sweet #50 were effective for longer than Sweet #45, with elevated antinociception from 60-120 minutes. Interestingly, the blends were significantly less effective in female mice, with only a few timepoints significantly increased over Vehicle treatment, and no significant differences in AUC (Figure 3B). This observation was confirmed by increasing the dose of the blends to 320 mg/kg, which produced no antinociception in female mice, suggesting the sex difference is not merely a potency/dose-related effect (Figure S1). Male-to-female comparison of AUC further supported this finding, with males significantly elevated over females for Sweet #50 (Figure 3C). This observation was unexpected as our previous work in individual terpenes did not indicate sex differences in neuropathic pain relief [31]. One caveat, however, is that the source of this main effect by sex cannot be distinguished across the three blends using this analytic approach; future work will be needed to answer this question.

Figure 3: Terpene Blends Relieve CIPN Neuropathic Pain Primarily in Male Mice.

Figure 3:

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Male and female CD-1 mice had CIPN induced and measured as described in the methods. Pre- and post-CIPN baselines (BL) were measured. Mice were injected with 200 mg/kg of one of the terpene blends or vehicle control (10% DMSO, 10% Tween80, 80% USP saline; i.p.). Data represented as the mean ± SEM. N = 8-10 mice/group. A) Male mice showed robust CIPN antinociception in their time course data, while B) female animals had a significantly lower elevation. Time course data were analyzed via 2-way ANOVA with Dunnett’s post hoc (Male ANOVA Drug F (3, 34) = 4.651, p = 0.0079; Female ANOVA Drug F (3, 36) = 3.208, p = 0.0344). Significance symbols indicate the comparison; # = Fruit #18 vs Vehicle, @ = Sweet #45 vs Vehicle, and * = Sweet #50 vs Vehicle. The number of symbols indicates the measured difference at the same timepoint; *p<0.05, **p<0.01, ***p<0.001, ****p<0.0001. The AUC data for male and female mice were calculated separately and are shown to the right. * = p<0.05 vs Vehicle by One-Way ANOVA with a Dunnett’s post hoc test (Male ANOVA F = 3.357, p = 0.03; Female ANOVA F = 1.018, p > 0.05). C) The AUC of male and female animals was combined and analyzed via 2-Way ANOVA with a Fisher’s LSD post hoc (ANOVA Sex F (1, 54) = 7.359, p = 0.0089), * = p<0.05 vs Males of the same group.

While the blends are complex, Myrcene is the primary terpene in both Fruit #18 and Sweet #50, while D-Limonene is the primary terpene in Sweet #45. We thus performed an experiment in CIPN with purified Myrcene and D-Limonene to see if we could recapitulate the effects of the blends with their respective primary terpene in male mice. Purified Myrcene did produce robust antinociception similar in magnitude to that of the Fruit #18 and Sweet #50 blends, suggesting the pain relief from those blends could be primarily driven by their Myrcene content (Figure 4). However, purified D-Limonene produced no measurable antinociception in this model (Figure 4). This suggests that the primary effect of Sweet #45 is not being driven by its primary terpene. However, we did note that the Sweet #45 had a lesser antinociceptive effect in Figure 3A; this may be due to the Limonene content of the blend having no efficacy in CIPN as we see in Figure 4.

Figure 4: β-Myrcene but not D-Limonene Recapitulates the Antinociception in its Dominant Blends.

Figure 4:

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Male CD-1 mice had CIPN induced and measured as described in the methods. Pre- and post-CIPN baselines (BL) were measured. Mice were injected with 200 mg/kg of purified β-Myrcene (dominant in Fruit #18 and Sweet #50), D-Limonene (dominant in Sweet #45), or vehicle control (10% DMSO, 10% Tween80, 80% USP saline; i.p.). Data represented as the mean ± SEM. N = 9–10 mice/group. **** = p < 0.0001 vs. same time point D-Limonene and Vehicle groups by RM 2-Way ANOVA with Dunnett’s post hoc test (ANOVA Drug F (2, 26) = 10.27, p = 0.0005). Myrcene produced robust antinociception, similar to its dominant blends Fruit #18 and Sweet #50, while Limonene had no efficacy, which may explain the lesser antinociception in Sweet #45, where Limonene is dominant.

Terpene Blends Evoke CIPN Antinociception via the Adenosine A2a Receptor

Our previous work showed that isolated terpenes evoke CIPN pain relief via the A2aR primarily in spinal cord [31]. To determine if the terpene blends also act on the A2aR to relieve CIPN pain, we used the A2aR antagonist istradefylline, as reported in our previous work; in that work we validated the dose we use here, 3.2 mg/kg [31]. We observed that the istradefylline treatment blocked the robust analgesic effects of the terpene blends in males (Figure 5A) and the minor analgesia observed in females (Figure 5B). Direct male-to-female comparison further supported this finding (Figure 5C). This suggests that these blends of terpenes are acting on the A2aR to induce analgesia for neuropathic pain, much like we observed for isolated single terpenes.

Figure 5: Terpene Blends Evoke CIPN Antinociception by the Adenosine A2a Receptor.

Figure 5:

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Male and female CD-1 mice had CIPN induced and measured as described in the Methods. Baseline (BL) mechanical thresholds were measured before and after CIPN. Mice were injected with istradefylline (3.2 mg/kg) followed 10 minutes later by 200 mg/kg of one of the terpene blends or Vehicle control (10% DMSO, 10% Tween80, 80% USP saline; i.p.). Data is shown as the mean ± SEM. N = 9-10 mice/group. The antagonist istradefylline blocked the robust antinociception from the terpene blends in A) male mice, and the minor antinociception in B) female mice. Time course data were analyzed via 2-Way ANOVA, no significant differences were observed (p > 0.05)(Male ANOVA Drug F (3, 32) = 1.728, p > 0.05; Female ANOVA Drug F (3, 36) = 1.941, p > 0.05). Male and female AUC data were analyzed separately (right) via One-Way ANOVA, no significant differences were observed (p > 0.05)(Male ANOVA F = 0.2967, p > 0.05; Female ANOVA F = 0.2226, p > 0.05) . C) No significant differences were observed when comparing the AUC from the time course data from male and female mice (p > 0.05)(ANOVA Sex F (1, 68) = 1.284, p > 0.05).

Discussion

In the present study, we investigated three terpene blends extracted from unique Cannabis chemovars to determine their effects on cannabimimetic and pain behaviors. We previously reported on the cannabimimetic and analgesic effects of individual terpenes, highlighting the potential differences in biological effects between blends of terpenes and isolated terpenes [13, 31]. Other studies have used various blends or mixes of terpenes, however, these blends were frequently mixed with cannabinoids or other chemical components and many were not rigorously quantitated as we’ve done here. Some of those studies did show that complex mixtures containing terpenes could relieve pain (reviewed in [15]). Overall, our study highlighted a fundamental similarity, in that all 3 terpene blends evoked cannabimimetic and CIPN antinociceptive behaviors via the A2aR, much like we previously reported for isolated terpenes [13, 31]. Limonene and β-Caryophyllene were significant components of our blends and have been reported to act on the A2aR, providing further support to our observations [21, 31, 32, 34], although we observed here that purified Limonene did not produce antinociception in CIPN. Despite these similarities, however, there were significant differences in our observations with terpene blends, most notably a major sex difference in CIPN antinociception.

We found that extracts Fruit #18, Sweet #45, and Sweet #50 had unique terpene profiles. This finding is consistent with previous work characterizing the difference in chemical makeup of various Cannabis strains [7, 10, 19]. Of the three extracts collected from Cannabis at Terpene Belt Farms, two shared a dominant terpene species with β-Myrcene in Fruit #18 and Sweet #50, and Limonene dominant in Sweet #45. Other terpenes in each extract comprised less than 20% of the weight volume of the sample (Figure 1). β-Myrcene and Limonene are frequently observed as the dominant terpene species in Cannabis [7, 10, 19]. However, terpene content analysis lacks standardization and can yield varying results [9]. β-Myrcene, a monoterpene, can break down into other bioactive monoterpenes, linalool and geraniol [15]. Both linalool and geraniol are antinociceptive via the adenosine A2a receptor (A2aR) in a CIPN mouse model, as we also observed in this study [31]. Injections of β-Myrcene have previously been shown to have antinociceptive activity in thermal pain assays (hot plate tests), while we show here that β-Myrcene is antinociceptive in CIPN (Figure 4). This hot plate antinociception was partially blocked with the μ-opioid receptor antagonist naloxone and completely blocked with the addition of the α-2 adrenergic receptor antagonist yohimbine [26]. Contrary to these previous studies, no significant difference in thermal latency between terpene blend and vehicle-treated animals was observed, despite all terpene blends containing β-Myrcene (Figure 2). This is consistent with our labs previous work on terpenes, in which we noted that the isolated terpenes we have tested are effective at relieving CIPN neuropathic pain, but poorly effective at relieving thermal pain in the tail flick assay [13, 31]. There is no research to date regarding the activity of β-Myrcene on the A2aR. There is one study suggesting β-Myrcene may be anxiolytic in zebrafish [36], though our work in mice suggests the blends with a higher concentration of β-Myrcene were anxiogenic (Figure 2).

Limonene was also a dominant terpene in the Sweet #45 blend, with measurable amounts in the other two blends. Studies on the effects of Limonene antinociception are limited, with some indicating effectiveness in relieving inflammatory pain [24], while others show it is ineffective for thermal pain, and may even increase thermal sensitivity [6]. Another study has noted Limonene as effective for sciatic nerve ligation neuropathic pain. However, only male rats were used in this study, so no sex differences were noted in the mechanical threshold [25]. In our neuropathic pain model, CIPN was relieved by administering the terpene blends in male but not female mice for all tested terpene blends (Figure 3). Meanwhile, our testing in this study suggests that D-Limonene is ineffective at relieving CIPN, which may have driven the lower antinociception of Sweet #45 (Figure 4). Limonene alone has been noted to regulate A2aR activity and this mechanism has been attributed to its anxiogenic, anti-inflammatory and anti-seizure effects [20, 21, 32]. We measured potential anxiogenic effects with the terpene blends we tested, including Sweet #45 (Figure 2). However, another study showed an intraperitoneal injection of 10 mg/kg Limonene alone was anxiolytic, and this effect was blocked by an A2aR antagonist, suggesting Limonene acts via A2aR to induce anxiolytic behaviors, although we did not observe this in our study [34]. Nonetheless, these studies provide evidence that limonene can activate the A2aR in other contexts, as we observed here, although our work suggests that Limonene cannot translate this A2aR activity into CIPN antinociception (Figure 4).

Other terpenes found in moderate concentrations in the blends we tested were α-Pinene found in terpene blends Fruit #18 and Sweet #50 at 15.66% and 13.22%, while Sweet #45 contained 4.12%. β-Caryophyllene was most abundant in Sweet #45 at 9.06% and Terpinolene/Fenchone in Sweet #50 at 18.88% (Figure 1). Both α-Pinene and β-Caryophyllene are anxiolytic in zebrafish [12]. β-Caryophyllene alone has been shown to elicit anxiolytic effects in rodents [3, 8, 17] and is effective at relieving neuropathic pain [1, 2]. We previously reported on the cannabimimetic and antinociceptive effects of β-Caryophyllene, and no sex differences were observed [13, 31]. There has been very little investigation on the effects of terpinolene and fenchone alone on pain, anxiety, and cannabimimetic effects. Due to the structure of these compounds, we were unable to differentiate them in the GC-FID analysis and are thus reported together. One study suggests a derivative of Fenchone, HU308, is antinociceptive in an osteoarthritis model and another reports terpinolene relieves Complete Freund’s Adjuvant (CFA) pain in a dose-dependent manner [5, 16].

The different terpene blends exhibited mostly similar cannabimimetic and antinociceptive behaviors, with the exception of Sweet #45, which had a lower duration of action in male mice in CIPN than the other two blends (Figure 3A), which may be driven by a lack of Limonene efficacy in CIPN (Figure 4). Fruit #18 and Sweet #50 had over half of their terpene content as β-Myrcene, versus Sweet #45 at 10.97%, which might further explain this difference. We also observed a striking sex difference, with all 3 blends markedly less effective in female mice. Other studies investigating these terpenes in neuropathic pain models either limited their investigation to male animals, or did not report a sex difference, as in our study with isolated terpenes [31]. In contrast, no sex difference was observed in cannabimimetic behaviors. At this point it is unclear why this sex difference was observed, or why it was not observed in our isolated terpene studies, and there is no evidence from the literature to formulate a hypothesis. It may be that the terpenes driving antinociception in the blends were different from those in our isolated terpene studies, and that those terpenes could have a sex difference (e.g., Myrcene). Future investigation will need to target this issue, including defined blends to work out when the sex difference manifests and from what terpenes, as well as investigation into the mechanism. Considering that most of the public consumes terpenes in complex mixture or extract forms, it will be critical to identify the reasons behind this sex difference and whether it translates to humans. Overall, these observations provide further support to the use of terpenes as effective non-opioid, non-cannabinoid therapeutics for chronic neuropathic pain.

Supplementary Material

1

Significance Statement.

This work demonstrates that complex terpene mixtures, similar to those consumed by the public, have cannabimimetic and antinociceptive effects via activation of the Adenosine A2a Receptor.

Acknowledgments

This work was funded by R01AT011517 to JMS. We would like to thank Drs. Tally Largent-Milnes and Todd Vanderah from the University of Arizona Comprehensive Center for Pain and Addiction for the use of their behavioral equipment. JMS is an equity holder in Teleport Pharmaceuticals, LLC and Botanical Results, LLC, and is further a consultant for Black Rock Nutraceuticals, LLC. Botanical Results and Black Rock Nutraceuticals are both involved in developing terpene products, however, none of these companies had any role in study funding, design, performance, or analysis. The authors have no other relevant conflicts of interest to declare.

Abbreviations:

A2aR

Adenosine A2a Receptor

AUC

Area Under the Curve

BL

Baseline

CBD

Cannabidiol

CFA

Complete Freund’s Adjuvant

CIPN

Chemotherapy Induced Peripheral Neuropathy

RM

Repeated Measures

THC

Δ9-tetrahydrocannabinol

Footnotes

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Data Availability

Any data that is needed to interpret the results is presented in this manuscript or in the supplementary data. However, our raw data is available upon request to the corresponding author, JMS.

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Associated Data

This section collects any data citations, data availability statements, or supplementary materials included in this article.

Supplementary Materials

1
NIHMS2069170-supplement-1.docx (817KB, docx)

Data Availability Statement

Any data that is needed to interpret the results is presented in this manuscript or in the supplementary data. However, our raw data is available upon request to the corresponding author, JMS.

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